Biofluid Collection and Filtration Device

ABSTRACT

A filtration device is disclosed for filtering debris from a biofluid sample. In at least one embodiment, the filtration device provides a collection container having a collection chamber defined by a flexible wall, a mouth fluidly communicating with the collection chamber and formed through the collection container at a top end, and a filter device defining a bottom of the collection chamber. A quantitative container has a quantitative chamber in fluid communication with the filter device with the filter device separating the collection chamber from the quantitative chamber. A biofluid sample is introduced into the collection chamber through the mouth, and when the mouth with a collection chamber cap, the flexible wall of the collection container is squeezed to reduce the volume of the collection chamber and force the biofluid sample through the filter device, the filtered biofluid sample thereafter being contained within the quantitative chamber.

RELATED APPLICATIONS

This is a continuation application and so claims the benefit pursuant to35 U.S.C. § 120 of a prior filed and co-pending U.S. non-provisionalpatent application Ser. No. 15/230,460, filed on Aug. 7, 2016, whichitself is a continuation-in-part of U.S. non-provisional patentapplication Ser. No. 14/484,207, filed on Sep. 11, 2014 (now U.S. Pat.No. 9,816,087), which claims priority pursuant to 35 U.S.C. § 119(e) toand is entitled to the filing dates of U.S. provisional patentapplication Ser. No. 61/982,322, filed on Apr. 21, 2014, and U.S.provisional patent application Ser. No. 61/876,778, filed on Sep. 12,2013. The contents of the aforementioned applications are incorporatedherein by reference.

BACKGROUND

Medical and other laboratories routinely process and handle variousbiofluid samples in order to conduct a wide range of assays. Forexample, immune-based assays can detect the presence or confirm theabsence of a specific antigen, antibody, or both. Similarly,polynucleotide-based assays can detect the presence or confirm theabsence of a specific genetic variant, or can measure the expressionlevels of specific genes. As another example, activity-based assays canbe performed in order to measure whether a specific molecule isfunctioning normally or not.

Although of great benefit, a biofluid sample typically cannot be assayeddirectly, in its crude form, and often must be processed in some mannerbefore meaningful analysis can take place. Many systems, devices, andmethods have been developed for the collection and purification ofbiofluid samples. However, these systems, devices, and methods areassociated with leakage which increases risk of contaminating thecollected sample as well increasing the risk of a user suffering adversehealth event upon exposure to leaked biofluid sample. Other potentialproblems encountered include cumulative variability introduced duringthe multiple sample transfer steps, loss or dilution of sample throughsample clinging or evaporation, introduction of contaminants, and/orsample misidentification. Lastly, these systems, devices, and methodsare not standardized for quantitative collection and cannot separate andisolate human cells from non-human components of a biofluid sample, suchas, e.g., viruses and bacteria.

The present specification discloses devices, methods and systems thatovercome the problems identified above. As disclosed herein, the deviceis self-contained and multi-functional which allows for the processingof a biofluid sample without the need of multiple sample transfer steps.In addition, the devices, methods and systems disclosed herein canisolate human cells from non-human components of a biofluid sample aswell as enabling rigorous and standardized quantitative collectionmetrics. Furthermore, the devices, methods and systems disclosed hereinallow for the direct interrogation of polynucleotides. These and otheradvantages will be disclosed herein.

SUMMARY

Aspects of the present specification disclose a filtration device. Thefiltration device disclosed herein is capable of quantitativecollection, separation of human and non-human components by means ofsize filtration, and the isolation of genetic material (DNA and/or RNA)from each component. The disclosed filtration devices may comprise acollection container comprising a collection chamber and a quantitativecontainer comprising a quantitative chamber, wherein the quantitativecontainer is removably attached to the collection container and whereinthe quantitative container is configured to move into the collectionchamber upon the application of force. The disclosed collectioncontainer comprises a filter device that upon an application of forceseparates the biofluid sample into a filtered component collected in thequantitative chamber and a retained component which remains in thecollection chamber. The disclosed filtration devices may also comprise acollection container comprising a quantitative container comprising aquantitative chamber and a plunger device, wherein the plunger device isremovably attached to the quantitative container and wherein the plungerdevice is configured to move into the quantitative chamber upon theapplication of force. In some aspects the plunger device comprises aplunger including a channel and a valve. In other aspects the plungerdevice comprises a plunger, a plunger filter, and a plunger chamber. Thedevice disclosed herein is suitable in any environment including pointof care use or in a clinical or laboratory setting.

Other aspects of the present specification disclose methods ofprocessing a biofluid sample using a filtration device disclosed herein.In some aspects, the method comprises the steps of depositing a biofluidsample into the collection chamber of the filtration device; andapplying a force to the filtration device whereby the biofluid samplepasses through the filter of the collection chamber, a defined volume offiltered biofluid sample is collected in the quantitative chamber, and aretained biofluid sample remains in the collection chamber. In someaspects, the method comprises the steps of depositing a biofluid sampleinto the collection chamber of the filtration device; applying a forceto the filtration device whereby the biofluid sample passes through thefilter of the collection chamber, a filtered biofluid sample iscollected in the quantitative chamber, and a retained biofluid sample ispresent in the collection chamber; removing the quantitative samplecomprising the filtered biofluid sample; attaching a plunger devicecomprising a plunger and a channel to the quantitative chamber; andprocessing the filtered biofluid sample by the addition of suitablereagents using the channel. In some aspects, the method comprises thesteps of depositing a biofluid sample into the collection chamber of thefiltration device; applying a force to the filtration device whereby thebiofluid sample passes through the filter of the collection chamber, afiltered biofluid sample is collected in a quantitative chamber, and aretained biofluid sample is present in the collection chamber; removingthe quantitative sample comprising the filtered biofluid sample;attaching a plunger device comprising a plunger and a channel to thequantitative chamber; processing the filtered biofluid sample by theaddition of suitable reagents using the channel; attaching the needledevice comprising a needle and porous filter to the quantitativechamber; and expelling the processes filtered biofluid sample from thequantitative chamber into a collection tube using the plunger.

In some aspects, the method comprises the steps of attaching acollection container comprising a biofluid sample to the filtrationdevice; transferring an amount of the biofluid sample to thequantitative chamber; removing the collection container from thefiltration device; and applying a force to the filtration device wherebythe biofluid sample passes through the quantitative filter of thequantitative container, a defined volume of filtered biofluid sample iscollected in the plunger chamber, and a retained biofluid sample remainsin the quantitative chamber. In some aspects, the method comprises thesteps of attaching a collection container comprising a biofluid sampleto the filtration device; transferring an amount of the biofluid sampleto the quantitative chamber; removing the collection container from thefiltration device; applying a force to the filtration device whereby thebiofluid sample is separated into two or more fractions within thequantitative chamber; and applying a force to the filtration devicewhereby the biofluid sample passes through the quantitative filter ofthe quantitative container, a filtered biofluid sample is collected inthe plunger chamber, and a retained biofluid sample remains in thequantitative chamber.

Other aspects of the present specification disclose systems forprocessing a biofluid sample. In some aspects, the system comprises acollection container, a quantitative container comprising a quantitativechamber and base, and a plunger device including a plunger, a channel,and a valve. The system may further comprise a waste container and/or aneedle device. In some aspects, the system comprises a collectioncontainer, a quantitative, a waste container, and a plunger deviceincluding a plunger, a channel and a valve, and a needle device. In someaspects, the system comprises a quantitative container including aquantitative chamber and a base including a needle; a base withoutneedle; a plunger device including a plunger, a plunger filter, and aplunger chamber. In some aspects, the system comprises a collectioncontainer; a quantitative container including a quantitative chamber anda base including a needle; a base without needle; a plunger deviceincluding a plunger, a plunger filter, and a plunger chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein.

FIG. 2 illustrates a telescopic perspective view of an embodiment for afiltration device disclosed herein.

FIG. 3 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein.

FIG. 4 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein.

FIG. 5 illustrates a telescopic perspective view of an embodiment for afiltration device disclosed herein.

FIG. 6 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein with FIG. 6A illustrating across-sectional view of an embodiment for a quantitative containerdisclosed herein attached to a plunger device disclosed herein and FIG.6B illustrating a cross-sectional view of an embodiment for a collectioncontainer disclosed herein.

FIG. 7 illustrates a telescopic perspective view of an embodiment for aquantitative container disclosed herein attached to a plunger devicedisclosed herein.

FIG. 8 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein.

FIG. 9 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein in operation with FIG. 9Aillustrating filtration device comprising collection container attachedto collection device and containing a biofluid sample and quantitationcontainer; FIG. 9B illustrating removal of collection device; FIG. 9Cillustrating closure of collection chamber by securement of collectionchamber cap; FIG. 9D illustrating filtered biofluid sample containedwithin quantitative chamber after application of force; FIG. 9Eillustrating removal of quantitative chamber containing filteredbiofluid sample from collection container containing retained biofluidsample; FIG. 9F illustrating attachment of plunger device and needledevice to quantitative container; and FIG. 9G illustrating expulsion ofbiofluid sample from quantitative container and retention of bead-boundpolynucleotide molecules in the chamber.

FIG. 10 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein in operation with FIG. 10Aillustrating filtration device comprising collection container attachedto collection device and containing a biofluid sample and quantitationcontainer; FIG. 10B illustrating removal of collection device; FIG. 10Cillustrating closure of collection chamber by securement of collectionchamber cap; FIG. 10D illustrating filtered biofluid sample containedwithin quantitative chamber after application of force; FIG. 10Eillustrating removal of quantitative chamber containing filteredbiofluid sample from collection container containing retained biofluidsample; FIG. 10F illustrating attachment of waste container tocollection container; FIG. 10G illustrating collection of remnantbiofluid sample within waste container after application of force; FIG.10H illustrating removal of collection chamber cap; FIG. 10Iillustrating addition of reagents to collection chamber; FIG. 10Jillustrating closure of collection chamber by securement of collectionchamber cap; and FIG. 10K illustrating collection of reagents withinwaste chamber after application of force.

FIG. 11 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein in operation with FIG. 11Aillustrating collection container having biofluid sample in collectionchamber and collection chamber cap secured; FIG. 11B illustratingremoval of collection chamber cap and attachment of quantitativecontainer having plunger device attached; FIG. 11C illustratinginversion of filtration device; FIG. 11D illustrating transfer ofdefined volume of biofluid sample to quantitative chamber; FIG. 11Eillustrating removal of collection container from quantitative containerhaving plunger device attached; FIG. 11F illustrating removal of base1054 having needle 1058 and attachment of base 1054 without needle; FIG.11G illustrating separation of fractions of biofluid sample aftercentrifugation; FIG. 11H illustrating filtered biofluid sample containedwithin plunger chamber after application of force; and FIG. 11Iillustrating removal of plunger device by unsecuring plunger attachment.

FIG. 12 illustrates a cross-sectional view of an embodiment for afiltration device disclosed herein in operation with FIG. 12Aillustrating filtration device comprising collection container attachedto collection device and containing a biofluid sample and quantitationcontainer; FIG. 12B illustrating removal of collection device andclosure of collection chamber by securement of collection chamber cap;FIG. 12C illustrating application of force by squeezing wall ofcollection container and passage of a filtered biofluid sample intoquantitative chamber after application of force; FIG. 12D illustratingremoval of quantitative chamber containing filtered biofluid sample fromcollection container containing retained biofluid sample; FIG. 12Eillustrating attachment of quantitative chamber cap; and FIG. 12Fillustrating dispensing of the biofluid sample 1216.

FIG. 13A illustrates a side view of an embodiment for a filtrationdevice disclosed herein in operation with FIG. 13B is a cross-sectionalview of the filtration device comprising a collection container attachedto collection device in the collection of a biofluid sample; FIG. 13C isa cross-sectional view of the filtration device illustrating containmentof a biofluid sample; FIG. 13D is a cross-sectional view of thefiltration device illustrating the instillation of the filtered biofluidsample to a lateral flow device.

The above described drawing figures illustrate aspects of the inventionin at least one of its exemplary embodiments, which are further definedin detail in the following description. Features, elements, and aspectsof the invention that are referenced by the same numerals in differentfigures represent the same, equivalent, or similar features, elements,or aspects, in accordance with one or more embodiments.

DETAILED DESCRIPTION

Currently, two major problems are associated with the use of oralsamples for diagnostic purposes. One involves the quantity and qualityof polynucleotide molecules necessary to perform pharmacogenomicapplications and the other involves the contaminating presents oforganisms associated with an infectious disease. These two problems arevery tightly interlinked in that addressing the problems associated withone exacerbates the problems associate with the other and vice versa.

Regarding the first, pharmacogenomic applications like genotyping orsequencing require large amounts of pure polynucleotide molecules forobtaining successful and accurate results. Historically, blood sampleshave been used as significantly greater amount of polynucleotidemolecules can be obtained relative to other biofluid samples likesaliva, buccal or urine samples. For example, a blood-derived samplecontains on the order of 100- to 1000-fold more amplifiable DNA, andproduces a significantly higher DMET genotyping call rate, relative tothe amount of amplifiable DNA obtained from a saliva-derived sample. Inaddition, the amount of host genomic DNA in an oral sample is only asmall percentage of the total DNA due to the presence of a large amountof bacteria. For example, studies have shown that the median percentageof bacterial DNA in mouthwash samples ranges from about 50-66% of thetotal DNA, while the median percentage of bacterial DNA increased to88.5% when cytobrush samples (i.e., swabbing) were used. Thus, thepurity of host DNA obtained from an oral sample is greatly reduced dueto the large amounts of contaminating DNA that interferes with andreduces the relative amount of host DNA.

Regarding the second, one of the key issues in diagnostic assays forinfectious disease is the ability to distinguish the presence of latentviruses from active viruses. A latent virus is one where the viral DNAhas integrated into the genomic DNA of the host cell and lies dormant ornon-infectious. An active virus is one that is replicating and releasingviral particles outside the cell and is virulent or infectious. Typicalbiofluid samples are collected in a manner that fails to separate cellsinfected with latent viruses from active viruses. As a consequence thereis a large degree of background noise due to the presence of latentviral DNA which contributes to a false positive result. Thus, there isno means of quantifying the level of infectious viral particles inassays that use biofluid samples like whole blood or saliva.

The present specification discloses a biofluid collection and filtrationdevice and methods and kits thereof that separate host cells from othercomponents or fractions of a biofluid sample. This allows, for examplethe separation of host cells from bacteria, thereby obtaining pure DNAfor pharmacogenomic applications. In addition, larger amounts of hostDNA can be obtained because cytobrush samples can be collected in orderto obtain more host cells. In addition, the disclosed device, methodsand kits enable the separation of host cells from active viralparticles. This allows increased sensitivity and accuracy in assays forinfectious diseases. Furthermore, the disclosed device, methods and kitsallow a measured volume of a biofluid sample to be collected, filteredand processed. This improves the sensitivity and accuracy of anysubsequent assay by standardizing the amount of a biofluid sample thatis analyzed.

The present specification discloses a filtration device useful forpurifying a crude biofluid sample including a blood sample, a urinesample or an oral sample like buccal or saliva. A filtration devicedisclosed herein may comprise a collection chamber, a quantitativechamber and/or a waste chamber. In operation, a crude biofluid sample isplaced inside a collection chamber of the filtration device disclosedherein and a collection chamber cap is secured over the opening toprovide a liquid-tight seal. Force is then applied to the filtrationdevice causing separation of the liquids of the crude sample from thesolids, such as, e.g., cells and particulate debris, using a filterlocated within the collection chamber. A defined volume of a cell-freeliquid fraction (or filtered biofluid sample) is collected in thequantitative chamber while the retained cell sample comprising hostcells remains in the collection chamber. The quantitative chamber isthen removed from the collection chamber and the filtered biofluidsample may then be further processed. To assist in such processing, aplunger device may be attached to the opening of the quantitativechamber. The plunger device includes a plunger with a central channelthat enables the addition of and the mixing of the reagents with thefiltered biofluid sample. Typical reagents include wash solutions, celllysis solutions, and/or buffered solutions. After processing, a needledevice including a filter is attached to the quantitative chamber whichenables the processes, filtered biofluid sample to be filtered onceagain as it is expelled from the quantitative chamber into a separatecollection device.

Upon removal of the quantitative chamber, the collection chambercontaining the retained cell sample may then be disposed of, or furtherprocessed. For further processing, a waste chamber may be attached tothe collection chamber and an appropriate reagent, such as a washsolution, a cell lysis solution, and/or buffered solution, may then beapplied to the collection chamber to further process the cells retainedon the filter. Force is then applied to the filtration device causingseparation of the liquid component of the reagent from the retainedsample using a filter located within the collection chamber. Anapplication of force includes manual manipulation of the filtrationdevice by a user or mechanical manipulation of the filtration device,such as, e.g., centrifugation.

Aspects of the present specification disclose a filtration device. Afiltration device disclosed herein provides for the filtration of abiofluid sample in order to separate the cellular and/or debris and/orcontaminants components from the liquid portion of a biofluid sample.The cell component retained on the filter can be processed forapplications such as genotyping, whereas the liquid, cell-free fractionis collected in the quantitative chamber and can be used in detectionassays for infectious disease. A filtration device disclosed herein maycomprise a collection container, a quantitative container, a wastecontainer, a plunger device, a needle device, or any combinationthereof. In some embodiments, the filtration device comprises acollection container and a quantitative container. In some embodiments,the filtration device comprises a collection container and a wastecontainer. In some embodiments, the filtration device comprises acollection container, a quantitative container, and a plunger device. Insome embodiments, the filtration device comprises a quantitativecontainer, a plunger device, and a needle device.

A filtration device disclosed herein is useful to process a wide varietyof biofluid samples. A wide variety of processes can take advantage ofthe filtration device disclosed herein, including, without limitation,purification, extraction, and/or assay processes. Non-limiting examplesof processing procedures that may be conducted using the filtrationdevice disclosed herein include separation of a sample from contaminantsand/or debris, separation of a solid biofluid sample component from aliquid biofluid sample component, purification or extraction of apolypeptide fraction, such as, e.g., antibodies, enzymes, toxins, orother protein group, from a biofluid sample, purification or extractionof a polynucleotide fraction, such as, e.g., DNA or RNA, from a biofluidsample, or purification or extraction of a chemical fraction from abiofluid sample. The resulting processed biofluid sample may then befurther processed, used as a read-out for an assay result, or used as areagent useful for conducting an experimental or assay. Biofluid samplesthat may be processed using the filtration device disclosed herein,including, without limitation, a saliva sample, a buccal sample, a urinesample, a fecal sample, a sperm sample, a vaginal sample, or a bloodsample such as, e.g., a whole blood sample, a plasma sample, or a serumsample.

The dimensions of a filtration device may be any suitable shape and sizeso long as the shape and size is useful for processing a biofluidsample. Typically, the shape and size of a filtration device disclosedherein will also allow for its functional placement into a centrifuge.In one embodiment, a filtration device disclosed herein is cylindricalin shape and of a size that enables placement of the filtration devicein a microcentrifuge, a table-top centrifuge and/or a free-standingcentrifuge. In some embodiments, a filtration device disclosed herein iscylindrical in shape and has a diameter of about 4 mm to about 15 mm anda length of about 5 mm to about 50 mm. In aspects of this embodiment, afiltration device disclosed herein is cylindrical in shape and has adiameter of, e.g., about 4 mm to about 6 mm, about 4 mm to about 8 mm,about 4 mm to about 10 mm, about 5 mm to about 7 mm, about 5 mm to about8 mm, about 5 mm to about 10 mm, about 6 mm to about 8 mm, about 6 mm toabout 9 mm, about 6 mm to about 10 mm, about 7 mm to about 8 mm, about 7mm to about 9 mm, about 7 mm to about 10 mm, or about 8 mm to about 10mm, and a length of, e.g., about 5 mm to about 10 mm, about 6 mm toabout 10 mm, about 6 mm to about 12 mm, about 8 mm to about 12 mm, about8 mm to about 15 mm, about 10 mm to about 15 mm, about 10 mm to about 20mm, about 10 mm to about 25 mm, about 10 mm to about 30 mm, about 15 mmto about 20 mm, about 15 mm to about 25 mm, about 15 mm to about 30 mm,about 20 mm to about 25 mm, about 20 mm to about 30 mm, about 20 mm toabout 35 mm, about 20 mm to about 40 mm, about 30 mm to about 40 mm,about 30 mm to about 45 mm, or about 30 mm to about 50 mm.

In other embodiments, a filtration device disclosed herein iscylindrical in shape and has a diameter of about 10 mm to about 20 mmand a length of about 50 mm to about 100 mm. In aspects of thisembodiment, a filtration device disclosed herein is cylindrical in shapeand has a diameter of, e.g., about 10 mm to about 12 mm, about 10 mm toabout 15 mm, about 10 mm to about 17 mm, about 12 mm to about 15 mm,about 12 mm to about 17 mm, about 12 mm to about 20 mm, about 15 mm toabout 18 mm, or about 15 mm to about 20 mm, and a length of, e.g., about50 mm to about 60 mm, about 50 mm to about 70 mm, about 50 mm to about80 mm, about 60 mm to about 70 mm, about 60 mm to about 80 mm, about 60mm to about 90 mm, about 70 mm to about 80 mm, about 70 mm to about 90mm, about 70 mm to about 100 mm, about 80 mm to about 90 mm, about 80 mmto about 100 mm, or about 90 mm to about 100 mm.

In other embodiments, a filtration device disclosed herein iscylindrical in shape and has a diameter of about 20 mm to about 40 mmand a length of about 80 mm to about 150 mm. In aspects of thisembodiment, a filtration device disclosed herein is cylindrical in shapeand has a diameter of, e.g., about 20 mm to about 25 mm, about 20 mm toabout 30 mm, about 20 mm to about 35 mm, about 25 mm to about 30 mm,about 25 mm to about 35 mm, about 25 mm to about 40 mm, about 30 mm toabout 35 mm, about 30 mm to about 40 mm, or about 35 mm to about 40 mm,and a length of, e.g., about 80 mm to about 90 mm, about 80 mm to about100 mm, about 80 mm to about 110 mm, about 90 mm to about 100 mm, about90 mm to about 110 mm, about 90 mm to about 120 mm, about 100 mm toabout 110 mm, about 100 mm to about 120 mm, about 100 mm to about 130mm, about 110 mm to about 120 mm, about 110 mm to about 130 mm, about110 mm to about 140 mm, about 120 mm to about 130 mm, about 120 mm toabout 140 mm, or about 120 mm to about 150 mm.

A filtration device disclosed herein may comprise, in part, a collectioncontainer. A collection container disclosed herein comprises acollection chamber for deposit of unprocessed biofluid sample. In someembodiments, a collection container disclosed herein comprises acollection chamber, a collection chamber cap, and a cap face seal. Insome embodiments, a collection container disclosed herein comprises acollection chamber, a collection chamber cap, a cap face seal and fingerrestraints. In some embodiments, a collection container disclosed hereincomprises a collection chamber, a collection chamber cap, a cap faceseal and a filter device.

The dimensions of a collection container may be any suitable shape andsize so long as the shape and size is useful for holding a biofluidsample deposited into the collection chamber. Typically, the shape andsize of a collection container disclosed herein will also allow for itsfunctional placement into a centrifuge. In one embodiment, a collectioncontainer disclosed herein is cylindrical in shape and of a size thatenables placement of the filtration device comprising the collectioncontainer in a microcentrifuge, a table-top centrifuge and/or afree-standing centrifuge. In some embodiments, a collection containerdisclosed herein is cylindrical in shape and has a diameter of about 4mm to about 10 mm and a length of about 5 mm to about 30 mm. In aspectsof this embodiment, a collection container disclosed herein iscylindrical in shape and has a diameter of, e.g., about 4 mm to about 6mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm, about 5 mm toabout 7 mm, about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6mm to about 8 mm, about 6 mm to about 9 mm, about 6 mm to about 10 mm,about 7 mm to about 8 mm, about 7 mm to about 9 mm, about 7 mm to about10 mm, or about 8 mm to about 10 mm, and a length of, e.g., about 5 mmto about 10 mm, about 6 mm to about 10 mm, about 6 mm to about 12 mm,about 8 mm to about 12 mm, about 8 mm to about 15 mm, about 10 mm toabout 15 mm, about 10 mm to about 20 mm, about 10 mm to about 25 mm,about 15 mm to about 20 mm, about 15 mm to about 25 mm, about 15 mm toabout 30 mm, about 20 mm to about 25 mm, or about 20 mm to about 30 mm.

In other embodiments, a collection container disclosed herein iscylindrical in shape and has a diameter of about 10 mm to about 20 mmand a length of about 50 mm to about 80 mm. In aspects of thisembodiment, a collection container disclosed herein is cylindrical inshape and has a diameter of, e.g., about 10 mm to about 12 mm, about 10mm to about 15 mm, about 10 mm to about 17 mm, about 12 mm to about 15mm, about 12 mm to about 17 mm, about 12 mm to about 20 mm, about 15 mmto about 18 mm, or about 15 mm to about 20 mm, and a length of, e.g.,about 50 mm to about 60 mm, about 50 mm to about 65 mm, about 50 mm toabout 70 mm, about 60 mm to about 70 mm, about 60 mm to about 75 mm,about 60 mm to about 80 mm, or about 70 mm to about 80 mm.

In other embodiments, a collection container disclosed herein iscylindrical in shape and has a diameter of about 20 mm to about 40 mmand a length of about 80 mm to about 120 mm. In aspects of thisembodiment, a collection container disclosed herein is cylindrical inshape and has a diameter of, e.g., about 20 mm to about 25 mm, about 20mm to about 30 mm, about 20 mm to about 35 mm, about 25 mm to about 30mm, about 25 mm to about 35 mm, about 25 mm to about 40 mm, about 30 mmto about 35 mm, about 30 mm to about 40 mm, or about 35 mm to about 40mm, and a length of, e.g., about 80 mm to about 90 mm, about 80 mm toabout 100 mm, about 80 mm to about 110 mm, about 90 mm to about 100 mm,about 90 mm to about 110 mm, about 90 mm to about 120 mm, about 100 mmto about 110 mm, about 100 mm to about 120 mm, or about 110 mm to about120 mm.

In other embodiments, a collection container disclosed herein designedto comprise rigid walls. In this design, external force is applied in amanner that moves a quantitation chamber into a collection chamber of acollection container. The resulting pressure developed inside acollection chamber forces a biofluid sample through a filter devicedisclosed herein where a filtered sample is collected in a quantitationchamber.

In other embodiments, a collection container disclosed herein designedto comprise flexible walls. In this design, external force is applied ina manner that squeezes the walls of the collection container. Theresulting pressure developed inside a collection chamber forces abiofluid sample through a filter device disclosed where a filteredsample is collected in a quantitation chamber.

A collection chamber is designed to hold a biofluid sample deposited bya user. The dimensions of a collection chamber may be any suitable shapeand size useful for holding a volume of biofluid sample sufficient forsubsequent processing and analysis. In one embodiment, a collectionchamber disclosed herein may have a defined volume capacity allowing forthe consistent collection of the same amount of a biofluid sample. Thisdefined volume capacity ensures that standardized quantitativecollection metrics can be achieved. In one embodiment, a collectionchamber disclosed herein may have a volume capacity of about 0.2 mL toabout 10.0 mL.

In aspects of this embodiment, a collection chamber disclosed herein mayhave a volume capacity of, e.g., about 0.2 mL, about 0.5 mL, about 0.75mL, about 1.0 mL, about 1.2 mL, or about 1.5 mL, about 2.0 mL, about 2.5mL, about 3.0 mL, about 3.5 mL, about 4.0 mL, about 4.5 mL, about 5.0mL, about 5.5 mL, about 6.0 mL, about 6.5 mL, about 7.0 mL, about 7.5mL, about 8.0 mL, about 8.5 mL, about 9.0 mL, about 9.5 mL, or about10.0 mL. In other aspects of this embodiment, a collection chamberdisclosed herein may have a volume capacity of, e.g., at least 0.2 mL,at least 0.5 mL, at least 0.75 mL, at least 1.0 mL, at least 1.2 mL, orat least 1.5 mL, at least 2.0 mL, at least 2.5 mL, at least 3.0 mL, atleast 3.5 mL, at least 4.0 mL, at least 4.5 mL, at least 5.0 mL, atleast 5.5 mL, at least 6.0 mL, at least 6.5 mL, at least 7.0 mL, atleast 7.5 mL, at least 8.0 mL, at least 8.5 mL, at least 9.0 mL, atleast 9.5 mL, or at least 10.0 mL. In yet other aspects of thisembodiment, a collection chamber disclosed herein may have a volumecapacity of, e.g., at most 0.2 mL, at most 0.5 mL, at most 0.75 mL, atmost 1.0 mL, at most 1.2 mL, or at most 1.5 mL, at most 2.0 mL, at most2.5 mL, at most 3.0 mL, at most 3.5 mL, at most 4.0 mL, at most 4.5 mL,at most 5.0 mL, at most 5.5 mL, at most 6.0 mL, at most 6.5 mL, at most7.0 mL, at most 7.5 mL, at most 8.0 mL, at most 8.5 mL, at most 9.0 mL,at most 9.5 mL, or at most 10.0 mL.

In still other aspects of this embodiment, a collection chamberdisclosed herein may have a volume capacity of, e.g., about 0.2 mL toabout 0.5 mL, about 0.2 mL to about 0.75 mL, about 0.2 mL to about 1.0mL, about 0.5 mL to about 0.75 mL, about 0.5 mL to about 1.0 mL, about0.5 mL to about 1.2 mL, about 0.5 mL to about 1.5 mL, about 0.75 mL toabout 1.0 mL, about 0.75 mL to about 1.2 mL, about 0.75 mL to about 1.5mL, about 0.75 mL to about 2.0 mL, about 1.0 mL to about 1.5 mL, about1.0 mL to about 2.0 mL, about 1.0 mL to about 2.5 mL, about 1.5 mL toabout 2.0 mL, about 1.5 mL to about 2.5 mL, about 1.5 mL to about 3.0mL, about 2.0 mL to about 2.5 mL, about 2.0 mL to about 3.0 mL, about2.0 mL to about 3.5 mL, about 2.5 mL to about 3.0 mL, about 2.5 mL toabout 3.5 mL, about 2.5 mL to about 4.0 mL, about 3.0 mL to about 3.5mL, about 3.0 mL to about 4.0 mL, about 3.0 mL to about 4.5 mL, about3.0 mL to about 5.0 mL, about 4.0 mL to about 5.0 mL, about 4.0 mL toabout 6.0 mL, about 5.0 mL to about 6.0 mL, about 5.0 mL to about 7.0mL, about 6.0 mL to about 7.0 mL, about 6.0 mL to about 8.0 mL, about7.0 mL to about 8.0 mL, about 7.0 mL to about 9.0 mL, about 8.0 mL toabout 10.0 mL, or about 9.0 mL to about 10.0 mL.

A collection container disclosed herein comprises, in part, a collectionchamber cap. A collection chamber cap disclosed herein provides aliquid-tight seal which prevents leakage of a biofluid sample containedwithin the collection chamber once the collection cap is secured to thecollection container. A collection chamber cap may be secured to acollection container by any mechanism that provides a liquid-tight sealwhich prevents leakage of a biofluid sample contained within thecollection chamber. In aspects of this embodiment, mechanisms useful forsecuring a collection chamber cap to the collection container includes,without limitation, a threaded screw mechanism, a pressure-lockmechanism, a snap-on mechanism, or a friction-fit mechanism. In someembodiments, a collection chamber cap is removable and enables a user toopen or close the collection chamber to the outside environment. In someembodiments, a collection chamber cap is non-removable.

A collection chamber cap disclosed herein may be attached to acollection container, such as, e.g., using a hinge attachment or a ringattachment. Alternatively, a collection chamber cap disclosed herein maybe unattached to a collection container, and thus completely removablefrom the collection container.

A collection container disclosed herein may further comprise, in part, afinger restraint. A finger restraint disclosed herein assists a user inadding or removing the collection container from, e.g., a quantitativecontainer disclosed herein, a waste container disclosed herein, and/or aplunger device disclosed herein. In function, the finger restraintprovides a mechanism of physical resistance in order for a user toachieve and/or maintain an appropriate grip on a collection container inorder to remove or add another component to it. The dimensions of afinger restraint may be any suitable shape and size so long as the shapeand size is useful for a user to achieve and/or maintain an appropriategrip on a collection container in order to remove or add anothercomponent to it. Non-limiting examples of a finger restraint includetabs, raised ridges, stippled or rough surface. In aspects of thisembodiment, a collection container may comprise, e.g., one or morefinger restraints, two or more finger restraints, three or more fingerrestraints, four or more finger restraints, or five or more fingerrestraints. In other aspects, a collection container may comprise, e.g.,about one to about two finger restraints, about one to about threefinger restraints, about one to about five finger restraints, about oneto about 10 finger restraints, about one to about 20 finger restraints,about one to about 30 finger restraints, about one to about 40 fingerrestraints, about one to about 50 finger restraints, about two to aboutthree finger restraints, about two to about five finger restraints,about two to about 10 finger restraints, about two to about 20 fingerrestraints, about two to about 30 finger restraints, about two to about40 finger restraints, about two to about 50 finger restraints, aboutfive to about 10 finger restraints, about five to about 20 fingerrestraints, about five to about 30 finger restraints, about five toabout 40 finger restraints, about five to about 50 finger restraints,about 10 to about 20 finger restraints, about 10 to about 30 fingerrestraints, about 10 to about 40 finger restraints, or about 10 to about50 finger restraints.

A filtration device disclosed herein may comprise, in part, a collectiondevice. A collection device disclosed herein provides assistance in thecollection of a crude biofluid sample and its placement into acollection chamber as disclosed herein. Placement of the sample may beaccomplished simply by having the individual from which the sample isbeing collected directly deposit the crude biofluid sample into thecollection chamber, such as, e.g., by spitting saliva, poring urine, orsqueezing blood droplets into the chamber. Alternatively, a collectiondevice may be employed to aid in the collection of a crude biofluidsample. For example, a funnel may be attached to the opening of acollection chamber disclosed herein to assist in the collection of thesample. In one aspect of this embodiment, a subject may spit into thefunnel and the sputum drip into the collection chamber. In anotheraspect of this embodiment, a subject or user may pour a biofluid sample,such as, e.g., a urine sample or blood sample, into the funnel from aseparate container and thereby fill the collection chamber with abiofluid sample. In some embodiments, a collection device comprises astrainer useful for preventing large particles or debris from enteringinto the collection chamber as well as a providing a physical object topress a swab or other collecting instrument in order to remove a crudebiofluid sample from the collecting instrument. In an aspect of thisembodiment, a cotton tip including a buccal swap can be pressed againsta strainer in order to deposit buccal material into the funnel. Asolution or buffer could then be used to rinse the cells into thecollection chamber.

A filtration device disclosed herein may comprises, in part, a filterdevice. A filter device provides the mechanism used to separate onecomponent or fraction of a biofluid sample from another component orfraction. In some embodiments, a filter device comprises a filter mount,a filter, and O-ring. In some embodiments, a filter device comprises afilter mount, a port, a filter, and O-ring. In some embodiments, afilter device comprises a filter mount, a one-way check valve, a filter,and O-ring. In some embodiments, a filter device comprises a filtermount, a port, a one-way check valve, a filter, and O-ring. A filterdevice disclosed herein may be incorporated into a collection containerdisclosed herein, a quantitative container disclosed herein, or a freelydetached and separate component.

In operation, after a biofluid sample is deposited into the collectionchamber and closed using the collection chamber cap, a user may applyforce in a manner that enables the biofluid components or fractions ofsufficient size or properties to pass through the filter and into thequantitative chamber. Alternatively, the filtration device comprisingthe collection container and quantitative container may have forceapplied by using a machine, such as, e.g., a microcentrifuge, atable-top centrifuge and/or a free-standing centrifuge.

In some embodiments, force is applied on a collection container in amanner that pushes a quantitative container disclosed herein into thecollection chamber. The resulting pressure developed inside a collectionchamber forces a biofluid sample through a filter device disclosedherein where a filtered sample is collected in a quantitation chamber.In other embodiments, force is applied in a manner that squeezes thewalls of the collection container. The resulting pressure developedinside a collection chamber forces a biofluid sample through a filterdevice disclosed where a filtered sample is collected in a quantitationchamber.

A filter disclosed herein enables the separation one component orfraction of a biofluid sample from another component or fraction. Forexample, a filter can enable the solid components, such as, e.g., cells,debris or contaminant, to be separated from the liquid components of thebiofluid sample. In aspects of this embodiment, a filter useful forseparating components contained in a biofluid sample can be, e.g., asize-exclusion filter, a plasma filter, an ion-exclusion filter, amagnetic filter, or an affinity filter. In other aspects of thisembodiment, a filter useful for separating components contained in abiofluid sample can have a pore size of, e.g., 0.1 μm, 0.2 μm, 0.5 μm,1.0 μm, 2.0 μm, 5.0 μm, 10.0 μm, 20.0 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70μm, 80 μm, 90 μm, 100 μm, or more. In yet other aspects of thisembodiment, a filter useful for separating components contained in abiofluid sample can have a pore size of, e.g., at least 0.2 μm, at least0.5 μm, at least 1.0 μm, at least 2.0 μm, at least 5.0 μm, at least 10.0μm, at least 20.0 μm, at least 30.0 μm, at least 40.0 μm, at least 50.0μm, at least 60.0 μm, at least 70.0 μm, at least 80.0 μm, at least 90.0μm, or at least 100.0 μm. In still other aspects of this embodiment, afilter useful for separating components contained in a biofluid samplecan have a pore size of, e.g., at most 0.1 μm, at most 0.2 μm, at most0.5 μm, at most 1.0 μm, at most 2.0 μm, at most 5.0 μm, at most 10.0 μm,at most 20.0 μm, at most 30.0 μm, at most 40.0 μm, at most 50.0 μm, atmost 60.0 μm, at most 70.0 μm, at most 80.0 μm, at most 90.0 μm, or atmost 100.0 μm. In other aspects of this embodiment, a filter useful forseparating components contained in a biofluid sample can have a poresize between, e.g., about 0.2 μm to about 0.5 μm, about 0.2 μm to about1.0 μm, about 0.2 μm to about 2.0 μm, about 0.2 μm to about 5.0 μm,about 0.2 μm to about 10.0 μm, about 0.2 μm to about 20.0 μm, about 0.2μm to about 30.0 μm, about 0.2 μm to about 40.0 μm, about 0.2 μm toabout 50.0 μm, about 0.5 μm to about 1.0 μm, about 0.5 μm to about 2.0μm, about 0.5 μm to about 5.0 μm, about 0.5 μm to about 10.0 μm, about0.5 μm to about 20.0 μm, about 0.5 μm to about 30.0 μm, about 0.5 μm toabout 40.0 μm, about 0.5 μm to about 50.0 μm, about 1.0 μm to about 2.0μm, about 1.0 μm to about 5.0 μm, about 1.0 μm to about 10.0 μm, about1.0 μm to about 20.0 μm, about 1.0 μm to about 30.0 μm, about 1.0 μm toabout 40.0 μm, about 1.0 μm to about 50.0 μm, about 2.0 μm to about 5.0μm, about 2.0 μm to about 10.0 μm, about 2.0 μm to about 20.0 μm, about2.0 μm to about 30.0 μm, about 2.0 μm to about 40.0 μm, about 2.0 μm toabout 50.0 μm, about 5.0 μm to about 10.0 μm, about 5.0 μm to about 20.0μm, about 5.0 μm to about 30.0 μm, about 5.0 μm to about 40.0 μm, about5.0 μm to about 50.0 μm, about 10.0 μm to about 20.0 μm, about 10.0 μmto about 30.0 μm, about 10.0 μm to about 40.0 μm, about 10.0 μm to about50.0 μm, about 10.0 μm to about 60.0 μm, about 10.0 μm to about 70.0 μm,about 20.0 μm to about 30.0 μm, about 20.0 μm to about 40.0 μm, about20.0 μm to about 50.0 μm, about 20.0 μm to about 60.0 μm, about 20.0 μmto about 70.0 μm, about 20.0 μm to about 80.0 μm, about 20.0 μm to about90.0 μm, about 20.0 μm to about 100.0 μm, about 30.0 μm to about 40.0μm, about 30.0 μm to about 50.0 μm, about 30.0 μm to about 60.0 μm,about 30.0 μm to about 70.0 μm, about 30.0 μm to about 80.0 μm, about30.0 μm to about 90.0 μm, about 30.0 μm to about 100.0 μm, about 40.0 μmto about 50.0 μm, about 40.0 μm to about 60.0 μm, about 40.0 μm to about70.0 μm, about 40.0 μm to about 80.0 μm, about 40.0 μm to about 90.0 μm,about 40.0 μm to about 100.0 μm, about 50.0 μm to about 60.0 μm, about50.0 μm to about 70.0 μm, about 50.0 μm to about 80.0 μm, about 50.0 μmto about 90.0 μm, or about 50.0 μm to about 100.0 μm.

In yet other aspects of this embodiment, a filter useful for separatingcomponents contained in a biofluid sample can be, e.g., an anion filteror a cation filter. In still other aspects of this embodiment, a filteruseful for separating components contained in a biofluid sample can be,e.g., an immune-affinity filter, an ion-affinity filter, apolynucleotide-affinity filter, a polypeptide-affinity filter, or achemical-affinity filter.

A filter mount and O-ring disclosed herein holds the filter in placewithin the collection container, provides a liquid tight seal betweenthe collection chamber and the quantitative chamber, and an attachmentpoint that enables a quantitative container or waste container disclosedherein to be secured to the collection container.

A port disclosed herein enables the release of air that would otherwisecreate a pressure build-up when a user applies force to the filtrationdevice causing a quantitative container disclosed herein to be pushed upinto the collection chamber. In some embodiments, a port disclosedherein is integrated into a filter mount disclosed herein. In someembodiments, a port disclosed herein is integrated into a filterdisclosed herein.

A one-way check valve disclosed herein enables a filtered biologicalsample passed into the quantitative chamber to flow back into thecollection chamber in situations where the volume of the filteredbiofluid sample surpasses the capacity of the defined volume of thequantitative chamber. A one-way check valve disclosed herein ensuresthat only the defined volume of a filtered biofluid sample is collectedin the quantitative chamber. In some embodiments, a one-way check valvedisclosed herein is integrated into a filter mount disclosed herein. Insome embodiments, a one-way check valve disclosed herein is integratedinto a filter disclosed herein.

A filtration device disclosed herein may comprise, in part, aquantitative container. A quantitative container disclosed hereinprovides for the collection of the biofluid sample component or fractionthat passes through the filter after application of an appropriateforce. For example, a quantitative container may be used to collect aliquid component or fraction of a biofluid sample passed through thefilter of the collection container. In some embodiments, a quantitativecontainer may comprise a quantitative chamber and a quantitative chamberdispenser. In some embodiments, a quantitative container may comprise aquantitative chamber and a quantitative chamber cap. In someembodiments, a quantitative container may comprise a quantitativechamber, a quantitative chamber dispenser, and a quantitative chambercap. In some embodiments, a quantitative container may comprise aquantitative chamber. In some embodiments, a quantitative container maycomprise a quantitative chamber and a base. In some embodiments, aquantitative container may comprise a quantitative chamber and a baseincluding a base needle.

The dimensions of a quantitative container may be any suitable shape andsize so long as the shape and size is useful for collecting a biofluidsample component or fraction filtered through the filter of thecollection container. Typically, the shape and size of a quantitativecontainer disclosed herein will also allow for its functional placementinto a centrifuge. In one embodiment, a quantitative container disclosedherein is cylindrical in shape and of a size that enables placement ofthe filtration device comprising the quantitative container in amicrocentrifuge, a table-top centrifuge and/or a free-standingcentrifuge. In some embodiments, a quantitative container disclosedherein is cylindrical in shape and has a diameter of about 4 mm to about10 mm and a length of about 5 mm to about 30 mm. In aspects of thisembodiment, a quantitative container disclosed herein is cylindrical inshape and has a diameter of, e.g., about 4 mm to about 6 mm, about 4 mmto about 8 mm, about 4 mm to about 10 mm, about 5 mm to about 7 mm,about 5 mm to about 8 mm, about 5 mm to about 10 mm, about 6 mm to about8 mm, about 6 mm to about 9 mm, about 6 mm to about 10 mm, about 7 mm toabout 8 mm, about 7 mm to about 9 mm, about 7 mm to about 10 mm, orabout 8 mm to about 10 mm, and a length of, e.g., about 5 mm to about 10mm, about 6 mm to about 10 mm, about 6 mm to about 12 mm, about 8 mm toabout 12 mm, about 8 mm to about 15 mm, about 10 mm to about 15 mm,about 10 mm to about 20 mm, about 10 mm to about 25 mm, about 15 mm toabout 20 mm, about 15 mm to about 25 mm, about 15 mm to about 30 mm,about 20 mm to about 25 mm, or about 20 mm to about 30 mm.

In other embodiments, a quantitative container disclosed herein iscylindrical in shape and has a diameter of about 10 mm to about 20 mmand a length of about 50 mm to about 80 mm. In aspects of thisembodiment, a quantitative container disclosed herein is cylindrical inshape and has a diameter of, e.g., about 10 mm to about 12 mm, about 10mm to about 15 mm, about 10 mm to about 17 mm, about 12 mm to about 15mm, about 12 mm to about 17 mm, about 12 mm to about 20 mm, about 15 mmto about 18 mm, or about 15 mm to about 20 mm, and a length of, e.g.,about 50 mm to about 60 mm, about 50 mm to about 65 mm, about 50 mm toabout 70 mm, about 60 mm to about 70 mm, about 60 mm to about 75 mm,about 60 mm to about 80 mm, or about 70 mm to about 80 mm.

In other embodiments, a quantitative container disclosed herein iscylindrical in shape and has a diameter of about 20 mm to about 40 mmand a length of about 80 mm to about 120 mm. In aspects of thisembodiment, a quantitative container disclosed herein is cylindrical inshape and has a diameter of, e.g., about 20 mm to about 25 mm, about 20mm to about 30 mm, about 20 mm to about 35 mm, about 25 mm to about 30mm, about 25 mm to about 35 mm, about 25 mm to about 40 mm, about 30 mmto about 35 mm, about 30 mm to about 40 mm, or about 35 mm to about 40mm, and a length of, e.g., about 80 mm to about 90 mm, about 80 mm toabout 100 mm, about 80 mm to about 110 mm, about 90 mm to about 100 mm,about 90 mm to about 110 mm, about 90 mm to about 120 mm, about 100 mmto about 110 mm, about 100 mm to about 120 mm, or about 110 mm to about120 mm.

In other embodiments, a quantitative container disclosed herein isdesigned to comprise rigid walls. In this design, external force isapplied in a manner that moves a quantitation chamber into a collectionchamber of a collection container. The resulting pressure developedinside a collection chamber forces a biofluid sample through a filterdevice disclosed herein where a filtered sample is collected in aquantitation chamber.

In other embodiments, a quantitative container disclosed herein designedto comprise flexible walls. In this design, an external force may beapplied in a manner that squeezes the walls of a quantitative container.The resulting pressure developed inside a quantitative chamber forces afiltered biofluid out of a quantitation chamber.

A quantitative chamber is designed to hold a biofluid sample componentor fraction deposited after an application of force. The dimensions of aquantitative chamber may be any suitable shape and size useful forholding a volume of biofluid sample component or fraction sufficient forsubsequent processing and analysis. In one embodiment, a quantitativechamber disclosed herein may have a defined volume capacity allowing forthe consistent collection of the same amount of a biofluid sample. Thisdefined volume capacity ensures that standardized quantitativecollection metrics can be achieved. In one embodiment, a quantitativechamber disclosed herein may have a volume capacity of about 0.2 mL toabout 10.0 mL.

In aspects of this embodiment, a quantitative chamber disclosed hereinmay have a volume capacity of, e.g., about 0.2 mL, about 0.5 mL, about0.75 mL, about 1.0 mL, about 1.2 mL, or about 1.5 mL, about 2.0 mL,about 2.5 mL, about 3.0 mL, about 3.5 mL, about 4.0 mL, about 4.5 mL,about 5.0 mL, about 5.5 mL, about 6.0 mL, about 6.5 mL, about 7.0 mL,about 7.5 mL, about 8.0 mL, about 8.5 mL, about 9.0 mL, about 9.5 mL, orabout 10.0 mL. In other aspects of this embodiment, a quantitativechamber disclosed herein may have a volume capacity of, e.g., at least0.2 mL, at least 0.5 mL, at least 0.75 mL, at least 1.0 mL, at least 1.2mL, or at least 1.5 mL, at least 2.0 mL, at least 2.5 mL, at least 3.0mL, at least 3.5 mL, at least 4.0 mL, at least 4.5 mL, at least 5.0 mL,at least 5.5 mL, at least 6.0 mL, at least 6.5 mL, at least 7.0 mL, atleast 7.5 mL, at least 8.0 mL, at least 8.5 mL, at least 9.0 mL, atleast 9.5 mL, or at least 10.0 mL. In yet other aspects of thisembodiment, a quantitative chamber disclosed herein may have a volumecapacity of, e.g., at most 0.2 mL, at most 0.5 mL, at most 0.75 mL, atmost 1.0 mL, at most 1.2 mL, or at most 1.5 mL, at most 2.0 mL, at most2.5 mL, at most 3.0 mL, at most 3.5 mL, at most 4.0 mL, at most 4.5 mL,at most 5.0 mL, at most 5.5 mL, at most 6.0 mL, at most 6.5 mL, at most7.0 mL, at most 7.5 mL, at most 8.0 mL, at most 8.5 mL, at most 9.0 mL,at most 9.5 mL, or at most 10.0 mL.

In still other aspects of this embodiment, a quantitative chamberdisclosed herein may have a volume capacity of, e.g., about 0.2 mL toabout 0.5 mL, about 0.2 mL to about 0.75 mL, about 0.2 mL to about 1.0mL, about 0.5 mL to about 0.75 mL, about 0.5 mL to about 1.0 mL, about0.5 mL to about 1.2 mL, about 0.5 mL to about 1.5 mL, about 0.75 mL toabout 1.0 mL, about 0.75 mL to about 1.2 mL, about 0.75 mL to about 1.5mL, about 0.75 mL to about 2.0 mL, about 1.0 mL to about 1.5 mL, about1.0 mL to about 2.0 mL, about 1.0 mL to about 2.5 mL, about 1.5 mL toabout 2.0 mL, about 1.5 mL to about 2.5 mL, about 1.5 mL to about 3.0mL, about 2.0 mL to about 2.5 mL, about 2.0 mL to about 3.0 mL, about2.0 mL to about 3.5 mL, about 2.5 mL to about 3.0 mL, about 2.5 mL toabout 3.5 mL, about 2.5 mL to about 4.0 mL, about 3.0 mL to about 3.5mL, about 3.0 mL to about 4.0 mL, about 3.0 mL to about 4.5 mL, about3.0 mL to about 5.0 mL, about 4.0 mL to about 5.0 mL, about 4.0 mL toabout 6.0 mL, about 5.0 mL to about 6.0 mL, about 5.0 mL to about 7.0mL, about 6.0 mL to about 7.0 mL, about 6.0 mL to about 8.0 mL, about7.0 mL to about 8.0 mL, about 7.0 mL to about 9.0 mL, about 8.0 mL toabout 10.0 mL, or about 9.0 mL to about 10.0 mL.

A quantitative container disclosed herein is designed to be removablyattached to a collection container disclosed herein which enables a userto freely attach or remove the quantitative container from thecollection container. In one embodiment, the quantitative container issecured to the filter mount of the filer device. Attachment of thequantitative container to a collection container provides a liquid-tightseal which prevents leakage of a biofluid sample during processing. Aquantitative container may be secured to a collection container by anymechanism that provides a liquid-tight seal which prevents leakage of abiofluid sample during processing. In aspects of this embodiment,mechanisms useful for securing a quantitative container to a collectioncontainer includes, without limitation, a threaded screw mechanism, apressure-lock mechanism, a snap-on mechanism, or a friction-fitmechanism.

A quantitative container disclosed herein may further comprise aquantitative chamber dispenser. A quantitative chamber dispenserdisclosed herein enables a filtered biofluid sample contained in aquantitative chamber to be dispensed into another container. Dispensingof a biofluid may be in a metered or quantitative manner or may beunmetered or qualitative in nature. A quantitative chamber dispenser maybe secured to a quantitative container by any mechanism that provides aliquid-tight seal which prevents leakage of a biofluid sample containedwithin the quantitative chamber. In aspects of this embodiment,mechanisms useful for securing a quantitative chamber dispenser to thequantitative container includes, without limitation, a threaded screwmechanism, a pressure-lock mechanism, a snap-on mechanism, or afriction-fit mechanism. In some embodiments, a quantitative chamberdispenser is removable and enables a user to open or close thequantitative chamber to the outside environment. A quantitative chamberdispenser disclosed herein may be attached to a quantitative container,such as, e.g., using a hinge attachment or a ring attachment.Alternatively, a quantitative chamber dispenser disclosed herein may beunattached to a quantitative container, and thus completely removablefrom the quantitative container.

A quantitative container disclosed herein may further comprise aquantitative chamber cap. A quantitative chamber cap disclosed hereinprovides a liquid-tight seal which prevents leakage of a biofluid samplecontained within the quantitative chamber. A quantitative chamber capmay be secured to a quantitative container or quantitative chamberdispenser by any mechanism that provides a liquid-tight seal whichprevents leakage of a biofluid sample contained within the quantitativechamber. In aspects of this embodiment, mechanisms useful for securing aquantitative chamber cap to the quantitative container or quantitativechamber dispenser includes, without limitation, a threaded screwmechanism, a pressure-lock mechanism, a snap-on mechanism, or afriction-fit mechanism. In some embodiments, a quantitative chamber capis removable and enables a user to open or close the quantitativechamber to the outside environment. A quantitative chamber cap disclosedherein may be attached to a quantitative container or quantitativechamber dispenser, such as, e.g., using a hinge attachment or a ringattachment. Alternatively, a quantitative chamber cap disclosed hereinmay be unattached to a quantitative container, and thus completelyremovable from the quantitative container or quantitative chamberdispenser.

A quantitative container disclosed herein may further comprise a base. Abase disclosed herein provides a liquid-tight seal which preventsleakage of a biofluid sample contained within the quantitative chamber.A base disclosed herein may be unremovable or removable. A removablebase may be secured to a quantitative container by any mechanism thatprovides a liquid-tight seal which prevents leakage of a biofluid samplecontained within the quantitative chamber. In aspects of thisembodiment, mechanisms useful for securing a removable base to thequantitative container includes, without limitation, a threaded screwmechanism, a pressure-lock mechanism, a snap-on mechanism, or afriction-fit mechanism. In some embodiments, a base is removable andenables a user to open or close the quantitative chamber to the outsideenvironment. A base disclosed herein may be attached to a quantitativecontainer, such as, e.g., using a hinge attachment or a ring attachment.Alternatively, a base disclosed herein may be unattached to aquantitative container, and thus completely removable from thequantitative container.

A base disclosed herein may further comprise a base needle. A baseneedle disclosed herein enables the transfer of a biofluid sample from acollection chamber disclosed herein to a quantitative chamber disclosedherein. In some embodiments, a base needle is used to pierce thecollection chamber cap of the collection container in order to transfera biofluid sample from collection chamber to the quantitative chamber.In some embodiments, a removable base comprising a base needle simplyreplaces a removable base currently attached to the quantitativecontainer.

The pore size of a base needle may be any suitable diameter or sizeuseful for transferring a biofluid sample from a collection chamberdisclosed herein to a quantitative chamber disclosed herein. In aspectsof this embodiment, a base needle has a pore size of, e.g., 18 gauge, 21gauge, 24 gauge, 27 gauge, or 30 gauge. In other aspects of thisembodiment, a base needle has a pore size diameter of, e.g., about 0.1mm, about 0.2, mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 2 mm,about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm,about 9 mm or about 10 mm. In yet other aspects of this embodiment, abase needle has a pore size diameter of, e.g., at least 0.1 mm, at least0.2, mm, at least 0.3 mm, at least 0.4 mm, at least 0.5 mm, at least 0.6mm, at least 0.7 mm, at least 0.8 mm, at least 0.9 mm, at least 1 mm, atleast 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm,at least 7 mm, at least 8 mm, at least 9 mm or at least 10 mm. In stillother aspects of this embodiment, a base needle has a pore size diameterof, e.g., at most 0.1 mm, at most 0.2, mm, at most 0.3 mm, at most 0.4mm, at most 0.5 mm, at most 0.6 mm, at most 0.7 mm, at most 0.8 mm, atmost 0.9 mm, at most 1 mm, at most 2 mm, at most 3 mm, at most 4 mm, atmost 5 mm, at most 6 mm, at most 7 mm, at most 8 mm, at most 9 mm or atmost 10 mm.

In other aspects of this embodiment, a base needle has a pore sizediameter between, e.g., about 0.1 mm to about 0.5 mm, about 0.1 mm toabout 1.0 mm, about 0.1 mm to about 5.0 mm, about 0.1 mm to about 10.0mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1.0 mm, about0.2 mm to about 5.0 mm, about 0.2 mm to about 10.0 mm, about 0.3 mm toabout 0.6 mm, about 0.3 mm to about 1.0 mm, about 0.3 mm to about 5.0mm, about 0.3 mm to about 10.0 mm, about 0.4 mm to about 0.7 mm, about0.4 mm to about 1.0 mm, about 0.4 mm to about 5.0 mm, about 0.4 mm toabout 10.0 mm, about 0.5 mm to about 1.0 mm, about 0.5 mm to about 5.0mm, about 0.5 mm to about 10.0 mm, about 1.0 mm to about 5.0 mm, about1.0 mm to about 10.0 mm, about 2.0 mm to about 5.0 mm, about 2.0 mm toabout 10.0 mm, or about 5.0 mm to about 10.0 mm.

In some embodiments, the base needle may comprise a base needle filter.A base needle filter provides the mechanism used to separate onecomponent or fraction of a biofluid sample from another component orfraction. For example, a base needle filter can retain purificationbeads within the quantitative chamber while allowing solutions used inprocessing the biologic sample to pass through the needle. The liquidcomponent is passed as waste while the bead-bound sample component orfraction is retained by the base needle filter in the collectionchamber. In aspects of this embodiment, a base needle filter useful forseparating components contained in a biofluid sample can be, e.g., asize-exclusion filter, a plasma filter, an ion-exclusion filter, amagnetic filter, or an affinity filter. In other aspects of thisembodiment, a base needle filter useful for separating componentscontained in a biofluid sample can have a pore size of, e.g., 0.2 μm,0.5 μm, 1.0 μm, 2.0 μm, 5.0 μm, 10.0 μm, or 20.0 μm. In yet otheraspects of this embodiment, a base needle filter useful for separatingcomponents contained in a biofluid sample can have a pore size of, e.g.,at least 0.2 μm, at least 0.5 μm, at least 1.0 μm, at least 2.0 μm, atleast 5.0 μm, at least 10.0 μm, or at least 20.0 μm. In still otheraspects of this embodiment, a base needle filter useful for separatingcomponents contained in a biofluid sample can have a pore size of, e.g.,at most 0.2 μm, at most 0.5 μm, at most 1.0 μm, at most 2.0 μm, at most5.0 μm, at most 10.0 μm, or at most 20.0 μm. In other aspects of thisembodiment, a base needle filter useful for separating componentscontained in a biofluid sample can have a pore size between, e.g., about0.2 μm to about 0.5 μm, about 0.2 μm to about 1.0 μm, about 0.2 μm toabout 2.0 μm, about 0.2 μm to about 5.0 μm, about 0.2 μm to about 10.0μm, about 0.2 μm to about 20.0 μm, about 0.2 μm to about 30.0 μm, about0.2 μm to about 40.0 μm, about 0.2 μm to about 50.0 μm, about 0.5 μm toabout 1.0 μm, about 0.5 μm to about 2.0 μm, about 0.5 μm to about 5.0μm, about 0.5 μm to about 10.0 μm, about 0.5 μm to about 20.0 μm, about0.5 μm to about 30.0 μm, about 0.5 μm to about 40.0 μm, about 0.5 μm toabout 50.0 μm, about 1.0 μm to about 2.0 μm, about 1.0 μm to about 5.0μm, about 1.0 μm to about 10.0 μm, about 1.0 μm to about 20.0 μm, about1.0 μm to about 30.0 μm, about 1.0 μm to about 40.0 μm, about 1.0 μm toabout 50.0 μm, about 2.0 μm to about 5.0 μm, about 2.0 μm to about 10.0μm, about 2.0 μm to about 20.0 μm, about 2.0 μm to about 30.0 μm, about2.0 μm to about 40.0 μm, about 2.0 μm to about 50.0 μm, about 5.0 μm toabout 10.0 μm, about 5.0 μm to about 20.0 μm, about 5.0 μm to about 30.0μm, about 5.0 μm to about 40.0 μm, about 5.0 μm to about 50.0 μm, about10.0 μm to about 20.0 μm, about 10.0 μm to about 30.0 μm, about 10.0 μmto about 40.0 μm, about 10.0 μm to about 50.0 μm, about 10.0 μm to about60.0 μm, about 10.0 μm to about 70.0 μm, about 20.0 μm to about 30.0 μm,about 20.0 μm to about 40.0 μm, about 20.0 μm to about 50.0 μm, about20.0 μm to about 60.0 μm, about 20.0 μm to about 70.0 μm, about 20.0 μmto about 80.0 μm, about 20.0 μm to about 90.0 μm, about 20.0 μm to about100.0 μm, about 30.0 μm to about 40.0 μm, about 30.0 μm to about 50.0μm, about 30.0 μm to about 60.0 μm, about 30.0 μm to about 70.0 μm,about 30.0 μm to about 80.0 μm, about 30.0 μm to about 90.0 μm, about30.0 μm to about 100.0 μm, about 40.0 μm to about 50.0 μm, about 40.0 μmto about 60.0 μm, about 40.0 μm to about 70.0 μm, about 40.0 μm to about80.0 μm, about 40.0 μm to about 90.0 μm, about 40.0 μm to about 100.0μm, about 50.0 μm to about 60.0 μm, about 50.0 μm to about 70.0 μm,about 50.0 μm to about 80.0 μm, about 50.0 μm to about 90.0 μm, or about50.0 μm to about 100.0 μm.

In yet other aspects of this embodiment, a base needle filter useful forseparating components contained in a biofluid sample can be, e.g., ananion filter or a cation filter. In still other aspects of thisembodiment, a base needle filter useful for separating componentscontained in a biofluid sample can be, e.g., an immune-affinity filter,an ion-affinity filter, a polynucleotide-affinity filter, apolypeptide-affinity filter, or a chemical-affinity filter.

A quantitative container disclosed herein may further comprise aquantitative filter. A quantitative filter disclosed herein provides amechanism used to separate one component or fraction of a biofluidsample from another component or fraction. In operation, after abiofluid sample is deposited into the collection chamber and closedusing the collection chamber cap, a user may apply force on thecollection chamber in a manner that transfers the biofluid components orfractions of sufficient size of properties to pass through thequantitative filter and into the quantitative chamber. Alternatively,the filtration device comprising the collection container andquantitative container may have force applied by using a machine, suchas, e.g., a microcentrifuge, a table-top centrifuge and/or afree-standing centrifuge.

A quantitative filter disclosed herein enables the separation onecomponent or fraction of a biofluid sample from another component orfraction. For example, a quantitative filter can enable the solidcomponents, such as, e.g., cells, debris or contaminant, to be separatedfrom the liquid components of the biofluid sample. In aspects of thisembodiment, a quantitative filter useful for separating componentscontained in a biofluid sample can be, e.g., a size-exclusion filter, aplasma filter, an ion-exclusion filter, a magnetic filter, or anaffinity filter. In other aspects of this embodiment, a quantitativefilter useful for separating components contained in a biofluid samplecan have a pore size of, e.g., 0.2 μm, 0.5 μm, 1.0 μm, 2.0 μm, 5.0 μm,10.0 μm, or 20.0 μm. In yet other aspects of this embodiment, aquantitative filter useful for separating components contained in abiofluid sample can have a pore size of, e.g., at least 0.2 μm, at least0.5 μm, at least 1.0 μm, at least 2.0 μm, at least 5.0 μm, at least 10.0μm, or at least 20.0 μm. In still other aspects of this embodiment, aquantitative filter useful for separating components contained in abiofluid sample can have a pore size of, e.g., at most 0.2 μm, at most0.5 μm, at most 1.0 μm, at most 2.0 μm, at most 5.0 μm, at most 10.0 μm,or at most 20.0 μm. In other aspects of this embodiment, a quantitativefilter useful for separating components contained in a biofluid samplecan have a pore size between, e.g., about 0.2 μm to about 0.5 μm, about0.2 μm to about 1.0 μm, about 0.2 μm to about 2.0 μm, about 0.2 μm toabout 5.0 μm, about 0.2 μm to about 10.0 μm, about 0.2 μm to about 20.0μm, about 0.2 μm to about 30.0 μm, about 0.2 μm to about 40.0 μm, about0.2 μm to about 50.0 μm, about 0.5 μm to about 1.0 μm, about 0.5 μm toabout 2.0 μm, about 0.5 μm to about 5.0 μm, about 0.5 μm to about 10.0μm, about 0.5 μm to about 20.0 μm, about 0.5 μm to about 30.0 μm, about0.5 μm to about 40.0 μm, about 0.5 μm to about 50.0 μm, about 1.0 μm toabout 2.0 μm, about 1.0 μm to about 5.0 μm, about 1.0 μm to about 10.0μm, about 1.0 μm to about 20.0 μm, about 1.0 μm to about 30.0 μm, about1.0 μm to about 40.0 μm, about 1.0 μm to about 50.0 μm, about 2.0 μm toabout 5.0 μm, about 2.0 μm to about 10.0 μm, about 2.0 μm to about 20.0μm, about 2.0 μm to about 30.0 μm, about 2.0 μm to about 40.0 μm, about2.0 μm to about 50.0 μm, about 5.0 μm to about 10.0 μm, about 5.0 μm toabout 20.0 μm, about 5.0 μm to about 30.0 μm, about 5.0 μm to about 40.0μm, about 5.0 μm to about 50.0 μm, about 10.0 μm to about 20.0 μm, about10.0 μm to about 30.0 μm, about 10.0 μm to about 40.0 μm, about 10.0 μmto about 50.0 μm, about 10.0 μm to about 60.0 μm, about 10.0 μm to about70.0 μm, about 20.0 μm to about 30.0 μm, about 20.0 μm to about 40.0 μm,about 20.0 μm to about 50.0 μm, about 20.0 μm to about 60.0 μm, about20.0 μm to about 70.0 μm, about 20.0 μm to about 80.0 μm, about 20.0 μmto about 90.0 μm, about 20.0 μm to about 100.0 μm, about 30.0 μm toabout 40.0 μm, about 30.0 μm to about 50.0 μm, about 30.0 μm to about60.0 μm, about 30.0 μm to about 70.0 μm, about 30.0 μm to about 80.0 μm,about 30.0 μm to about 90.0 μm, about 30.0 μm to about 100.0 μm, about40.0 μm to about 50.0 μm, about 40.0 μm to about 60.0 μm, about 40.0 μmto about 70.0 μm, about 40.0 μm to about 80.0 μm, about 40.0 μm to about90.0 μm, about 40.0 μm to about 100.0 μm, about 50.0 μm to about 60.0μm, about 50.0 μm to about 70.0 μm, about 50.0 μm to about 80.0 μm,about 50.0 μm to about 90.0 μm, or about 50.0 μm to about 100.0 μm.

In yet other aspects of this embodiment, a quantitative filter usefulfor separating components contained in a biofluid sample can be, e.g.,an anion filter or a cation filter. In still other aspects of thisembodiment, a filter useful for separating components contained in abiofluid sample can be, e.g., an immune-affinity filter, an ion-affinityfilter, a polynucleotide-affinity filter, a polypeptide-affinity filter,or a chemical-affinity filter.

A filtration device disclosed herein may comprise, in part, a plungerdevice. A plunger device disclosed herein enables the addition of and/orthe mixing of reagents with a biofluid sample component or fractioncontained in the quantitative chamber. In some embodiments, a plungerdevice comprises a plunger including a plunger O-ring and a plungerattachment. In some embodiments, a plunger device comprises a plungerincluding a plunger O-ring, a plunger filter, and a plunger attachment.In some embodiments, a plunger device comprises a plunger including aplunger O-ring, a plunger filter, a plunger chamber, and a plungerattachment. In some embodiments, a plunger device comprises a plungerincluding a plunger O-ring, a plunger filter, and a plunger attachment.In some embodiments, a plunger device comprises a plunger including aplunger O-ring, a plunger filter, a plunger chamber, and a plungerattachment including a plunger attachment face seal. In someembodiments, a plunger device comprises a plunger including a plungerO-ring and a plunger attachment including a plunger attachment faceseal. In some embodiments, a plunger device comprises a plungerincluding a channel and a plunger O-ring, and a plunger attachmentincluding a plunger attachment face seal. In some embodiments, a plungerdevice comprises a plunger including a channel, a valve and a plungerO-ring, and a plunger attachment including a plunger attachment faceseal.

A plunger is a piston-like device that may be mechanically moved up anddown the length of the quantitative chamber. The plunger O-ring of theplunger forms a liquid tight seal that prevents leakage of the biofluidsample from the quantitative chamber. A plunger may further comprise achannel. A channel disclosed herein is a lumen that connects aquantitative chamber disclosed herein to the outside environment andenables a user to add a reagent into the quantitative chamber. Afteraddition of reagent, a user can force the plunger into the quantitativechamber which allows for the mixing of the reagent with the biofluidsample. The valve, located at one end of the channel allows the releaseof air pressure when pulling the plunger back up from the down position.

In some embodiments, the plunger device further comprises a plungerfilter. A plunger filter provides the mechanism used to separate onecomponent or fraction of a biofluid sample from another component orfraction. For example, a plunger filter can enable the solid components,such as, e.g., cells, debris or contaminant, to be separated from theliquid components of the biofluid sample. The liquid component is passedinto the plunger chamber while the solid component is retained by theplunger filter in the quantitative chamber. In aspects of thisembodiment, a plunger filter useful for separating components containedin a biofluid sample can be, e.g., a size-exclusion filter, a plasmafilter, an ion-exclusion filter, a magnetic filter, or an affinityfilter. In other aspects of this embodiment, a plunger filter useful forseparating components contained in a biofluid sample can have a poresize of, e.g., 0.2 μm, 0.5 μm, 1.0 μm, 2.0 μm, 5.0 μm, 10.0 μm, or 20.0μm. In yet other aspects of this embodiment, a plunger filter useful forseparating components contained in a biofluid sample can have a poresize of, e.g., at least 0.2 μm, at least 0.5 μm, at least 1.0 μm, atleast 2.0 μm, at least 5.0 μm, at least 10.0 μm, or at least 20.0 μm. Instill other aspects of this embodiment, a plunger filter useful forseparating components contained in a biofluid sample can have a poresize of, e.g., at most 0.2 μm, at most 0.5 μm, at most 1.0 μm, at most2.0 μm, at most 5.0 μm, at most 10.0 μm, or at most 20.0 μm. In otheraspects of this embodiment, a plunger filter useful for separatingcomponents contained in a biofluid sample can have a pore size between,e.g., about 0.2 μm to about 0.5 μm, about 0.2 μm to about 1.0 μm, about0.2 μm to about 2.0 μm, about 0.2 μm to about 5.0 μm, about 0.2 μm toabout 10.0 μm, about 0.2 μm to about 20.0 μm, about 0.2 μm to about 30.0μm, about 0.2 μm to about 40.0 μm, about 0.2 μm to about 50.0 μm, about0.5 μm to about 1.0 μm, about 0.5 μm to about 2.0 μm, about 0.5 μm toabout 5.0 μm, about 0.5 μm to about 10.0 μm, about 0.5 μm to about 20.0μm, about 0.5 μm to about 30.0 μm, about 0.5 μm to about 40.0 μm, about0.5 μm to about 50.0 μm, about 1.0 μm to about 2.0 μm, about 1.0 μm toabout 5.0 μm, about 1.0 μm to about 10.0 μm, about 1.0 μm to about 20.0μm, about 1.0 μm to about 30.0 μm, about 1.0 μm to about 40.0 μm, about1.0 μm to about 50.0 μm, about 2.0 μm to about 5.0 μm, about 2.0 μm toabout 10.0 μm, about 2.0 μm to about 20.0 μm, about 2.0 μm to about 30.0μm, about 2.0 μm to about 40.0 μm, about 2.0 μm to about 50.0 μm, about5.0 μm to about 10.0 μm, about 5.0 μm to about 20.0 μm, about 5.0 μm toabout 30.0 μm, about 5.0 μm to about 40.0 μm, about 5.0 μm to about 50.0μm, about 10.0 μm to about 20.0 μm, about 10.0 μm to about 30.0 μm,about 10.0 μm to about 40.0 μm, about 10.0 μm to about 50.0 μm, about10.0 μm to about 60.0 μm, about 10.0 μm to about 70.0 μm, about 20.0 μmto about 30.0 μm, about 20.0 μm to about 40.0 μm, about 20.0 μm to about50.0 μm, about 20.0 μm to about 60.0 μm, about 20.0 μm to about 70.0 μm,about 20.0 μm to about 80.0 μm, about 20.0 μm to about 90.0 μm, about20.0 μm to about 100.0 μm, about 30.0 μm to about 40.0 μm, about 30.0 μmto about 50.0 μm, about 30.0 μm to about 60.0 μm, about 30.0 μm to about70.0 μm, about 30.0 μm to about 80.0 μm, about 30.0 μm to about 90.0 μm,about 30.0 μm to about 100.0 μm, about 40.0 μm to about 50.0 μm, about40.0 μm to about 60.0 μm, about 40.0 μm to about 70.0 μm, about 40.0 μmto about 80.0 μm, about 40.0 μm to about 90.0 μm, about 40.0 μm to about100.0 μm, about 50.0 μm to about 60.0 μm, about 50.0 μm to about 70.0μm, about 50.0 μm to about 80.0 μm, about 50.0 μm to about 90.0 μm, orabout 50.0 μm to about 100.0 μm.

In yet other aspects of this embodiment, a plunger filter useful forseparating components contained in a biofluid sample can be, e.g., ananion filter or a cation filter. In still other aspects of thisembodiment, a plunger filter useful for separating components containedin a biofluid sample can be, e.g., an immune-affinity filter, anion-affinity filter, a polynucleotide-affinity filter, apolypeptide-affinity filter, or a chemical-affinity filter.

A plunger device further comprises a plunger chamber. A plunger chamberdisclosed herein provides for the collection of a biofluid samplecomponent or fraction that passes through the plunger filter afterapplication of an appropriate force. For example, a plunger chamber maybe used to collect a liquid component or fraction of a biofluid samplepassed through the plunger filter of the quantitative chamber. Thedimensions of a plunger chamber may be any suitable shape and sizeuseful for holding a volume of biofluid sample component or fractionsufficient for subsequent processing and analysis. In one embodiment, aplunger chamber disclosed herein may have a defined volume capacityallowing for the consistent collection of the same amount of a biofluidsample. This defined volume capacity ensures that standardizedquantitative collection metrics can be achieved. In one embodiment, aplunger chamber disclosed herein may have a volume capacity of about 0.2mL to about 10.0 mL.

In aspects of this embodiment, a plunger chamber disclosed herein mayhave a volume capacity of, e.g., about 0.2 mL, about 0.5 mL, about 0.75mL, about 1.0 mL, about 1.2 mL, or about 1.5 mL, about 2.0 mL, about 2.5mL, about 3.0 mL, about 3.5 mL, about 4.0 mL, about 4.5 mL, about 5.0mL, about 5.5 mL, about 6.0 mL, about 6.5 mL, about 7.0 mL, about 7.5mL, about 8.0 mL, about 8.5 mL, about 9.0 mL, about 9.5 mL, or about10.0 mL. In other aspects of this embodiment, a plunger chamberdisclosed herein may have a volume capacity of, e.g., at least 0.2 mL,at least 0.5 mL, at least 0.75 mL, at least 1.0 mL, at least 1.2 mL, orat least 1.5 mL, at least 2.0 mL, at least 2.5 mL, at least 3.0 mL, atleast 3.5 mL, at least 4.0 mL, at least 4.5 mL, at least 5.0 mL, atleast 5.5 mL, at least 6.0 mL, at least 6.5 mL, at least 7.0 mL, atleast 7.5 mL, at least 8.0 mL, at least 8.5 mL, at least 9.0 mL, atleast 9.5 mL, or at least 10.0 mL. In yet other aspects of thisembodiment, a plunger chamber disclosed herein may have a volumecapacity of, e.g., at most 0.2 mL, at most 0.5 mL, at most 0.75 mL, atmost 1.0 mL, at most 1.2 mL, or at most 1.5 mL, at most 2.0 mL, at most2.5 mL, at most 3.0 mL, at most 3.5 mL, at most 4.0 mL, at most 4.5 mL,at most 5.0 mL, at most 5.5 mL, at most 6.0 mL, at most 6.5 mL, at most7.0 mL, at most 7.5 mL, at most 8.0 mL, at most 8.5 mL, at most 9.0 mL,at most 9.5 mL, or at most 10.0 mL.

In still other aspects of this embodiment, a plunger chamber disclosedherein may have a volume capacity of, e.g., about 0.2 mL to about 0.5mL, about 0.2 mL to about 0.75 mL, about 0.2 mL to about 1.0 mL, about0.5 mL to about 0.75 mL, about 0.5 mL to about 1.0 mL, about 0.5 mL toabout 1.2 mL, about 0.5 mL to about 1.5 mL, about 0.75 mL to about 1.0mL, about 0.75 mL to about 1.2 mL, about 0.75 mL to about 1.5 mL, about0.75 mL to about 2.0 mL, about 1.0 mL to about 1.5 mL, about 1.0 mL toabout 2.0 mL, about 1.0 mL to about 2.5 mL, about 1.5 mL to about 2.0mL, about 1.5 mL to about 2.5 mL, about 1.5 mL to about 3.0 mL, about2.0 mL to about 2.5 mL, about 2.0 mL to about 3.0 mL, about 2.0 mL toabout 3.5 mL, about 2.5 mL to about 3.0 mL, about 2.5 mL to about 3.5mL, about 2.5 mL to about 4.0 mL, about 3.0 mL to about 3.5 mL, about3.0 mL to about 4.0 mL, about 3.0 mL to about 4.5 mL, about 3.0 mL toabout 5.0 mL, about 4.0 mL to about 5.0 mL, about 4.0 mL to about 6.0mL, about 5.0 mL to about 6.0 mL, about 5.0 mL to about 7.0 mL, about6.0 mL to about 7.0 mL, about 6.0 mL to about 8.0 mL, about 7.0 mL toabout 8.0 mL, about 7.0 mL to about 9.0 mL, about 8.0 mL to about 10.0mL, or about 9.0 mL to about 10.0 mL.

A plunger device disclosed herein is designed to be removably attachedto a quantitation container disclosed herein via the plunger attachmentwhich enables a user to freely attach or remove the plunger device fromthe quantitative container. Attachment of the plunger device to aquantitative container provides a liquid-tight seal which preventsleakage of a biofluid sample during processing. A plunger device may besecured to a quantitative container by any mechanism that provides aliquid-tight seal which prevents leakage of a biofluid sample duringprocessing. In aspects of this embodiment, mechanisms useful forsecuring a plunger device to a quantitative container includes, withoutlimitation, a threaded screw mechanism, a pressure-lock mechanism, asnap-on mechanism, or a friction-fit mechanism.

A filtration device disclosed herein may comprise, in part, a needledevice. A needle device disclosed herein may be attached to aquantitative container as disclosed herein and provides a mechanism fora biofluid sample component or fraction to be removed from aquantitative chamber. In some embodiments, a needle device may beattached to the bottom of a quantitative container disclosed herein andenable some components of a biofluid sample contained within thequantitative chamber to be expelled using the plunder, while retainingother components.

A needle device disclosed herein may further comprise a needle. A needledisclosed herein enables the removal of a biofluid sample from aquantitative chamber disclosed herein. In some embodiments, a needle isused to pierce the base of the quantitative container in order totransfer a biofluid sample contained within the quantitative chamber.

The pore size of a needle may be any suitable diameter or size usefulfor transferring a biofluid sample from a collection chamber disclosedherein to a quantitative chamber disclosed herein. In aspects of thisembodiment, a needle has a pore size of, e.g., 18 gauge, 21 gauge, 24gauge, 27 gauge, or 30 gauge. In other aspects of this embodiment, aneedle has a pore size diameter of, e.g., about 0.1 mm, about 0.2, mm,about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm,about 0.8 mm, about 0.9 mm, about 1 mm, about 2 mm, about 3 mm, about 4mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm or about10 mm. In yet other aspects of this embodiment, a needle has a pore sizediameter of, e.g., at least 0.1 mm, at least 0.2, mm, at least 0.3 mm,at least 0.4 mm, at least 0.5 mm, at least 0.6 mm, at least 0.7 mm, atleast 0.8 mm, at least 0.9 mm, at least 1 mm, at least 2 mm, at least 3mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least8 mm, at least 9 mm or at least 10 mm. In still other aspects of thisembodiment, a needle has a pore size diameter of, e.g., at most 0.1 mm,at most 0.2, mm, at most 0.3 mm, at most 0.4 mm, at most 0.5 mm, at most0.6 mm, at most 0.7 mm, at most 0.8 mm, at most 0.9 mm, at most 1 mm, atmost 2 mm, at most 3 mm, at most 4 mm, at most 5 mm, at most 6 mm, atmost 7 mm, at most 8 mm, at most 9 mm or at most 10 mm.

In other aspects of this embodiment, a needle has a pore size diameterbetween, e.g., about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1.0mm, about 0.1 mm to about 5.0 mm, about 0.1 mm to about 10.0 mm, about0.2 mm to about 0.5 mm, about 0.2 mm to about 1.0 mm, about 0.2 mm toabout 5.0 mm, about 0.2 mm to about 10.0 mm, about 0.3 mm to about 0.6mm, about 0.3 mm to about 1.0 mm, about 0.3 mm to about 5.0 mm, about0.3 mm to about 10.0 mm, about 0.4 mm to about 0.7 mm, about 0.4 mm toabout 1.0 mm, about 0.4 mm to about 5.0 mm, about 0.4 mm to about 10.0mm, about 0.5 mm to about 1.0 mm, about 0.5 mm to about 5.0 mm, about0.5 mm to about 10.0 mm, about 1.0 mm to about 5.0 mm, about 1.0 mm toabout 10.0 mm, about 2.0 mm to about 5.0 mm, about 2.0 mm to about 10.0mm, or about 5.0 mm to about 10.0 mm.

In some embodiments, a needle device disclosed herein further comprisesa needle filter. In some embodiments, a needle filter disclosed hereinin located within the needle disclosed herein. A needle filter providesthe mechanism used to separate one component or fraction of a biofluidsample from another component or fraction. For example, a needle filtercan enable the solid components, such as, e.g., cells, debris orcontaminant, to be separated from the liquid components of the biofluidsample. The liquid component is passed into the quantitative chamberwhile the solid component is retained by the needle filter in thecollection chamber. As another example, a needle filter enables theseparation of the liquid component of a biofluid sample from solidcomponents, such as, e.g., polynucleotide molecules like DNA and RNA.The liquid component is expelled from the quantitative chamber while thesolid component is retained by the needle filter in the quantitativechamber. In aspects of this embodiment, a needle filter useful forseparating components contained in a biofluid sample can be, e.g., asize-exclusion filter, a plasma filter, an ion-exclusion filter, amagnetic filter, or an affinity filter. In other aspects of thisembodiment, a needle filter useful for separating components containedin a biofluid sample can have a pore size of, e.g., 0.2 μm, 0.5 μm, 1.0μm, 2.0 μm, 5.0 μm, 10.0 μm, or 20.0 μm. In yet other aspects of thisembodiment, a needle filter useful for separating components containedin a biofluid sample can have a pore size of, e.g., at least 0.2 μm, atleast 0.5 μm, at least 1.0 μm, at least 2.0 μm, at least 5.0 μm, atleast 10.0 μm, or at least 20.0 μm. In still other aspects of thisembodiment, a needle filter useful for separating components containedin a biofluid sample can have a pore size of, e.g., at most 0.2 μm, atmost 0.5 μm, at most 1.0 μm, at most 2.0 μm, at most 5.0 μm, at most10.0 μm, or at most 20.0 μm. In other aspects of this embodiment, aneedle filter useful for separating components contained in a biofluidsample can have a pore size between, e.g., about 0.2 μm to about 0.5 μm,about 0.2 μm to about 1.0 μm, about 0.2 μm to about 2.0 μm, about 0.2 μmto about 5.0 μm, about 0.2 μm to about 10.0 μm, about 0.2 μm to about20.0 μm, about 0.2 μm to about 30.0 μm, about 0.2 μm to about 40.0 μm,about 0.2 μm to about 50.0 μm, about 0.5 μm to about 1.0 μm, about 0.5μm to about 2.0 μm, about 0.5 μm to about 5.0 μm, about 0.5 μm to about10.0 μm, about 0.5 μm to about 20.0 μm, about 0.5 μm to about 30.0 μm,about 0.5 μm to about 40.0 μm, about 0.5 μm to about 50.0 μm, about 1.0μm to about 2.0 μm, about 1.0 μm to about 5.0 μm, about 1.0 μm to about10.0 μm, about 1.0 μm to about 20.0 μm, about 1.0 μm to about 30.0 μm,about 1.0 μm to about 40.0 μm, about 1.0 μm to about 50.0 μm, about 2.0μm to about 5.0 μm, about 2.0 μm to about 10.0 μm, about 2.0 μm to about20.0 μm, about 2.0 μm to about 30.0 μm, about 2.0 μm to about 40.0 μm,about 2.0 μm to about 50.0 μm, about 5.0 μm to about 10.0 μm, about 5.0μm to about 20.0 μm, about 5.0 μm to about 30.0 μm, about 5.0 μm toabout 40.0 μm, about 5.0 μm to about 50.0 μm, about 10.0 μm to about20.0 μm, about 10.0 μm to about 30.0 μm, about 10.0 μm to about 40.0 μm,about 10.0 μm to about 50.0 μm, about 10.0 μm to about 60.0 μm, about10.0 μm to about 70.0 μm, about 20.0 μm to about 30.0 μm, about 20.0 μmto about 40.0 μm, about 20.0 μm to about 50.0 μm, about 20.0 μm to about60.0 μm, about 20.0 μm to about 70.0 μm, about 20.0 μm to about 80.0 μm,about 20.0 μm to about 90.0 μm, about 20.0 μm to about 100.0 μm, about30.0 μm to about 40.0 μm, about 30.0 μm to about 50.0 μm, about 30.0 μmto about 60.0 μm, about 30.0 μm to about 70.0 μm, about 30.0 μm to about80.0 μm, about 30.0 μm to about 90.0 μm, about 30.0 μm to about 100.0μm, about 40.0 μm to about 50.0 μm, about 40.0 μm to about 60.0 μm,about 40.0 μm to about 70.0 μm, about 40.0 μm to about 80.0 μm, about40.0 μm to about 90.0 μm, about 40.0 μm to about 100.0 μm, about 50.0 μmto about 60.0 μm, about 50.0 μm to about 70.0 μm, about 50.0 μm to about80.0 μm, about 50.0 μm to about 90.0 μm, or about 50.0 μm to about 100.0μm.

In yet other aspects of this embodiment, a needle filter useful forseparating components contained in a biofluid sample can be, e.g., ananion filter or a cation filter. In still other aspects of thisembodiment, a needle filter useful for separating components containedin a biofluid sample can be, e.g., an immune-affinity filter, anion-affinity filter, a polynucleotide-affinity filter, apolypeptide-affinity filter, or a chemical-affinity filter.

A filtration device disclosed herein may comprise, in part, a wastechamber. A waste chamber disclosed herein provides for the collection ofreagents used to process the biofluid sample retained in the collectionchamber after filtration. For example, a waste chamber may be used tocollect wash solutions used to wash cells retained in the collectionchamber after filtration of a crude biofluid sample.

The dimensions of a waste chamber may be any suitable shape and size solong as the shape and size is useful for collecting a biofluid samplecomponent or fraction filtered through the filter of the collectionchamber. Typically, the shape and size of a collection chamber disclosedherein will also allow for its functional placement into a centrifuge.In one embodiment, a waste chamber disclosed herein is cylindrical inshape and of a size that enables placement of the filtration devicecomprising the waste chamber in a microcentrifuge, a table-topcentrifuge and/or a free-standing centrifuge. In some embodiments, awaste chamber disclosed herein is cylindrical in shape and has adiameter of about 4 mm to about 10 mm and a length of about 5 mm toabout 30 mm. In aspects of this embodiment, a waste chamber disclosedherein is cylindrical in shape and has a diameter of, e.g., about 4 mmto about 6 mm, about 4 mm to about 8 mm, about 4 mm to about 10 mm,about 5 mm to about 7 mm, about 5 mm to about 8 mm, about 5 mm to about10 mm, about 6 mm to about 8 mm, about 6 mm to about 9 mm, about 6 mm toabout 10 mm, about 7 mm to about 8 mm, about 7 mm to about 9 mm, about 7mm to about 10 mm, or about 8 mm to about 10 mm, and a length of, e.g.,about 5 mm to about 10 mm, about 6 mm to about 10 mm, about 6 mm toabout 12 mm, about 8 mm to about 12 mm, about 8 mm to about 15 mm, about10 mm to about 15 mm, about 10 mm to about 20 mm, about 10 mm to about25 mm, about 15 mm to about 20 mm, about 15 mm to about 25 mm, about 15mm to about 30 mm, about 20 mm to about 25 mm, or about 20 mm to about30 mm.

In other embodiments, a waste chamber disclosed herein is cylindrical inshape and has a diameter of about 10 mm to about 20 mm and a length ofabout 50 mm to about 80 mm. In aspects of this embodiment, a wastechamber disclosed herein is cylindrical in shape and has a diameter of,e.g., about 10 mm to about 12 mm, about 10 mm to about 15 mm, about 10mm to about 17 mm, about 12 mm to about 15 mm, about 12 mm to about 17mm, about 12 mm to about 20 mm, about 15 mm to about 18 mm, or about 15mm to about 20 mm, and a length of, e.g., about 50 mm to about 60 mm,about 50 mm to about 65 mm, about 50 mm to about 70 mm, about 60 mm toabout 70 mm, about 60 mm to about 75 mm, about 60 mm to about 80 mm, orabout 70 mm to about 80 mm.

In other embodiments, a waste chamber disclosed herein is cylindrical inshape and has a diameter of about 20 mm to about 40 mm and a length ofabout 80 mm to about 120 mm. In aspects of this embodiment, a wastechamber disclosed herein is cylindrical in shape and has a diameter of,e.g., about 20 mm to about 25 mm, about 20 mm to about 30 mm, about 20mm to about 35 mm, about 25 mm to about 30 mm, about 25 mm to about 35mm, about 25 mm to about 40 mm, about 30 mm to about 35 mm, about 30 mmto about 40 mm, or about 35 mm to about 40 mm, and a length of, e.g.,about 80 mm to about 90 mm, about 80 mm to about 100 mm, about 80 mm toabout 110 mm, about 90 mm to about 100 mm, about 90 mm to about 110 mm,about 90 mm to about 120 mm, about 100 mm to about 110 mm, about 100 mmto about 120 mm, or about 110 mm to about 120 mm.

A waste chamber is designed to hold a biofluid sample component orfraction deposited after an application of force. The dimensions of awaste chamber may be any suitable shape and size useful for holding avolume of biofluid sample sufficient for subsequent processing andanalysis. In one embodiment, a waste chamber disclosed herein may have adefined volume capacity allowing for the consistent collection of thesame amount of a sample. This defined volume capacity ensures thatstandardized quantitative collection metrics can be achieved. In oneembodiment, a waste chamber disclosed herein may have a volume capacityof about 0.2 mL to about 10.0 mL.

In aspects of this embodiment, a waste chamber disclosed herein may havea volume capacity of, e.g., about 0.2 mL, about 0.5 mL, about 0.75 mL,about 1.0 mL, about 1.2 mL, or about 1.5 mL, about 2.0 mL, about 2.5 mL,about 3.0 mL, about 3.5 mL, about 4.0 mL, about 4.5 mL, about 5.0 mL,about 5.5 mL, about 6.0 mL, about 6.5 mL, about 7.0 mL, about 7.5 mL,about 8.0 mL, about 8.5 mL, about 9.0 mL, about 9.5 mL, or about 10.0mL. In other aspects of this embodiment, a waste chamber disclosedherein may have a volume capacity of, e.g., at least 0.2 mL, at least0.5 mL, at least 0.75 mL, at least 1.0 mL, at least 1.2 mL, or at least1.5 mL, at least 2.0 mL, at least 2.5 mL, at least 3.0 mL, at least 3.5mL, at least 4.0 mL, at least 4.5 mL, at least 5.0 mL, at least 5.5 mL,at least 6.0 mL, at least 6.5 mL, at least 7.0 mL, at least 7.5 mL, atleast 8.0 mL, at least 8.5 mL, at least 9.0 mL, at least 9.5 mL, or atleast 10.0 mL. In yet other aspects of this embodiment, a waste chamberdisclosed herein may have a volume capacity of, e.g., at most 0.2 mL, atmost 0.5 mL, at most 0.75 mL, at most 1.0 mL, at most 1.2 mL, or at most1.5 mL, at most 2.0 mL, at most 2.5 mL, at most 3.0 mL, at most 3.5 mL,at most 4.0 mL, at most 4.5 mL, at most 5.0 mL, at most 5.5 mL, at most6.0 mL, at most 6.5 mL, at most 7.0 mL, at most 7.5 mL, at most 8.0 mL,at most 8.5 mL, at most 9.0 mL, at most 9.5 mL, or at most 10.0 mL.

In still other aspects of this embodiment, a waste chamber disclosedherein may have a volume capacity of, e.g., about 0.2 mL to about 0.5mL, about 0.2 mL to about 0.75 mL, about 0.2 mL to about 1.0 mL, about0.5 mL to about 0.75 mL, about 0.5 mL to about 1.0 mL, about 0.5 mL toabout 1.2 mL, about 0.5 mL to about 1.5 mL, about 0.75 mL to about 1.0mL, about 0.75 mL to about 1.2 mL, about 0.75 mL to about 1.5 mL, about0.75 mL to about 2.0 mL, about 1.0 mL to about 1.5 mL, about 1.0 mL toabout 2.0 mL, about 1.0 mL to about 2.5 mL, about 1.5 mL to about 2.0mL, about 1.5 mL to about 2.5 mL, about 1.5 mL to about 3.0 mL, about2.0 mL to about 2.5 mL, about 2.0 mL to about 3.0 mL, about 2.0 mL toabout 3.5 mL, about 2.5 mL to about 3.0 mL, about 2.5 mL to about 3.5mL, about 2.5 mL to about 4.0 mL, about 3.0 mL to about 3.5 mL, about3.0 mL to about 4.0 mL, about 3.0 mL to about 4.5 mL, about 3.0 mL toabout 5.0 mL, about 4.0 mL to about 5.0 mL, about 4.0 mL to about 6.0mL, about 5.0 mL to about 6.0 mL, about 5.0 mL to about 7.0 mL, about6.0 mL to about 7.0 mL, about 6.0 mL to about 8.0 mL, about 7.0 mL toabout 8.0 mL, about 7.0 mL to about 9.0 mL, about 8.0 mL to about 10.0mL, or about 9.0 mL to about 10.0 mL.

A waste chamber disclosed herein is designed to be removably attached toa collection chamber disclosed herein which enables a user to freelyattach or remove the waste chamber from the collection chamber. In oneembodiment, the waste chamber is secured to the filter mount of thecollection chamber. Attachment of the waste chamber to a collectionchamber provides a liquid-tight seal which prevents leakage of abiofluid sample during processing. A waste chamber may be secured to acollection chamber by any mechanism that provides a liquid-tight sealwhich prevents leakage of a biofluid sample during processing. Inaspects of this embodiment, mechanisms useful for securing a wastechamber to a collection chamber includes, without limitation, a threadedscrew mechanism, a pressure-lock mechanism, a snap-on mechanism, or afriction-fit mechanism.

In one embodiment, filtration device 10 comprises collection container20 and quantitative container 50 (FIG. 1). Collection container 20comprises collection chamber 22, cap face seal 24, and filter device 40comprising filter mount 42, filter 44, port 46, and filter mount O-ring48 (FIG. 1). In an aspect of this embodiment, collection chamber cap 26is attached via hinged mechanism 27 to collection container 20. FIG. 1also illustrates the placement of collection device 30 comprisingstrainer 32 to collection container 20. Quantitative container 50comprises quantitative chamber 52 and base 54 (FIG. 1). A telescopicperspective view of this embodiment is shown in FIG. 2.

In another embodiment, filtration device 310 comprises quantitativecontainer 350 and plunger device 360 (FIG. 3). Quantitative container350 comprises quantitative chamber 352 and base 354 (FIG. 3). Plungerdevice 360 comprises plunger 362, channel 364, valve 366, plunger O-ring368, plunger attachment 370 and plunger attachment face seal 372 (FIG.3).

In another embodiment, filtration device 410 comprises quantitativecontainer 450, plunger device 460, and needle device 480 (FIG. 4).Quantitative container 450 comprises quantitative chamber 452 and base454 (FIG. 4). Plunger device 460 comprises plunger 462, channel 464,valve 466, plunger O-ring 468, plunger attachment 470 and plungerattachment face seal 472 (FIG. 4). Needle device 480 comprises needle482 and needle filter 484 (FIG. 4). A telescopic perspective view ofthis embodiment is shown in FIG. 5.

In another embodiment, filtration device 610 comprises collectioncontainer 620, quantitative container 650, and plunger device 660 (FIG.6A). Collection container 620 comprises collection chamber 622, cap faceseal 624, and finger restraint 628 (FIG. 6B). In an aspect of thisembodiment, collection chamber cap 626 is attached via screw mechanism629 to collection container 620. Quantitative container 650 comprisesquantitative chamber 652, quantitative filter 653, and base 654comprising base O-ring 655, base face seal 656, and base needle 658 withneedle 659 (FIG. 6B). Plunger device 660 comprises plunger 662, plungerchamber 663, plunger O-ring 668, plunger attachment 670 and plungerfilter 674 (FIG. 6A). A telescopic perspective view of this embodimentis shown in FIG. 7.

In another embodiment, filtration device 810 comprises collectioncontainer 820 and quantitative container 850 (FIG. 8). Collectioncontainer 820 comprises collection chamber 822 and filter device 840(FIG. 8). FIG. 8 also illustrates the placement of collection device 830to collection container 820. Quantitative container 850 comprisesquantitative chamber 852 and base (FIG. 8).

Aspects of the present specification disclose, in part, a samplecollection system or kit. A sample collection system or kit disclosedherein may comprise a collection chamber disclosed herein, aquantitative chamber disclosed herein, a waste chamber disclosed herein,a plunger device disclosed herein, a needle device disclosed herein oneor more bottles containing processing reagents, and/or any combinationthereof. In aspects of this embodiment, a processing reagent disclosedherein includes, without limitation, a wash solution, a lysis solution,a buffered solution, an elution solution, or any combination thereof.

In some embodiments, a sample collection system or kit comprises acollection chamber disclosed herein, a quantitative chamber disclosedherein, a waste chamber disclosed herein, a plunger device disclosedherein, and a needle device disclosed herein. In some embodiments, asample collection system or kit comprises a collection chamber disclosedherein, a quantitative chamber disclosed herein, a waste chamberdisclosed herein, a plunger device disclosed herein, a needle devicedisclosed herein, and one or more bottles containing processing reagentsincluding, without limitation, a wash solution, a lysis solution, abuffered solution, an elution solution, or any combination thereof.

In some embodiments, a sample collection system or kit comprises acollection chamber disclosed herein, a quantitative chamber disclosedherein, a plunger device disclosed herein, and a needle device disclosedherein. In some embodiments, a sample collection system or kit comprisesa collection chamber disclosed herein, a quantitative chamber disclosedherein, a plunger device disclosed herein, and a needle device disclosedherein, and one or more bottles containing processing reagentsincluding, without limitation, a wash solution, a lysis solution, abuffered solution, an elution solution, or any combination thereof.

In some embodiments, a sample collection system or kit comprises acollection chamber disclosed herein, a quantitative chamber disclosedherein, and a waste chamber disclosed herein. In some embodiments, asample collection system or kit comprises a collection chamber disclosedherein, a quantitative chamber disclosed herein, and a waste chamberdisclosed herein, and one or more bottles containing processing reagentsincluding, without limitation, a wash solution, a lysis solution, abuffered solution, an elution solution, or any combination thereof.

Aspects of the present specification disclose, in part, a method ofprocessing a biofluid sample using a filtration device disclosed herein.The device disclosed herein is designed to be used in any environmentincluding point of care use as well as clinical and laboratory settings.

In some embodiments, a method of processing a biofluid sample using afiltration device comprises the steps of a) depositing a biofluid sampleinto the collection chamber of the filtration device; and b) applying aforce to the filtration device whereby the biofluid sample passesthrough the filter of the collection chamber, a filtered biofluid sampleis collected in a quantitative chamber, and a retained biofluid sampleis present in the collection chamber.

In some embodiments, a method of processing a biofluid sample using afiltration device comprises the steps of a) depositing a biofluid sampleinto the collection chamber of the filtration device; and b) applying aforce to the filtration device whereby the biofluid sample passesthrough the filter of the collection chamber, a filtered biofluid sampleis collected in a quantitative chamber, and a retained biofluid sampleis present in the collection chamber; c) removing the quantitativesample comprising the filtered biofluid sample; d) attaching a plungerdevice comprising a plunger and a channel to the quantitative chamber;and e) processing the filtered biofluid sample by the addition ofsuitable reagents using the channel. In aspects of these embodiments,step (e) may be repeated one or more times with the same or differentreagents.

In some embodiments, a method of processing a biofluid sample using afiltration device comprises the steps of a) depositing a biofluid sampleinto the collection chamber of the filtration device; and b) applying aforce to the filtration device whereby the biofluid sample passesthrough the filter of the collection chamber, a filtered biofluid sampleis collected in a quantitative chamber, and a retained biofluid sampleis present in the collection chamber; c) removing the quantitativesample comprising the filtered biofluid sample; d) attaching a plungerdevice comprising a plunger and a channel to the quantitative chamber;e) processing the filtered biofluid sample by the addition of suitablereagents using the channel; f) attaching the needle device comprising aneedle and porous filter to the quantitative chamber; and g) expellingthe processes filtered biofluid sample from the quantitative chamberinto a collection tube using the plunger. In aspects of theseembodiments, step (e) may be repeated one or more times with the same ordifferent reagents.

In some embodiments, a method of processing a biofluid sample using afiltration device comprises the steps of a) depositing a biofluid sampleinto the collection chamber of the filtration device; and b) applying aforce to the filtration device whereby the biofluid sample passesthrough the filter of the collection chamber, a filtered biofluid sampleis collected in a quantitative chamber, and a retained biofluid sampleis present in the collection chamber; c) removing the quantitativesample comprising the filtered biofluid sample; d) attaching a wastechamber to the collection chamber; and e) adding reagents to thecollection chamber; and e) applying a force to the filtration devicewhereby the reagents passes through the filter of the collection chamberand collected in the waste chamber and a processed, retained biofluidsample is present in the collection chamber. In aspects of theseembodiments, step (e) may be repeated one or more times with the same ordifferent reagents.

In one embodiment, a method of processing a biofluid sample using afiltration device 910 comprises the step of depositing biofluid sample912 into collection chamber 922 of collection container 920 usingcollection device 930 (FIG. 9A). After depositing biofluid sample 912 tocollection chamber 922, collection device 930 is removed (FIG. 9B) andcollection chamber cap 926 is secured to collection container 920 (FIG.9C). Force is then applied to filtration device 910 in a manner thatpushes quantitate container 950 into collection chamber 922 (FIG. 9D).The application of force pushes biofluid sample 912 through filterdevice 940 thereby separating components or fractions of biofluid sample912 into a defined volume of filtered components or fraction 916collected in quantitative chamber 952 and retained biofluid samplecomprising host cells 914 remains in collection chamber 922 (FIG. 9D).Quantitative container 850 is then removed from collection container 920(FIG. 9E) and plunger device 960 and needle device 980 are attached toquantitative container 950 (FIG. 9F). The application of force toplunger device 960 pushes filtered biofluid sample 916 though needlefilter 982 further purifying filtered biofluid sample 916 (FIG. 9G).

In another embodiment, a method of processing a biofluid sample using afiltration device 1010 comprises the step of depositing biofluid sample1012 into collection chamber 1022 of collection container 1020 usingcollection device 1030 (FIG. 10A). After depositing biofluid sample 1012to collection chamber 1022, collection device 1030 is removed (FIG. 10B)and collection chamber cap 1026 is secured to collection container 1020(FIG. 10C). Force is then applied to filtration device 1010 in a mannerthat pushes quantitate container 1050 into collection chamber 1022 (FIG.10D). The application of force pushes biofluid sample 1012 throughfilter device 1040 thereby separating components or fractions ofbiofluid sample 1012 into a defined volume of filtered components orfraction 1016 collected in quantitative chamber 1052 and retainedbiofluid sample comprising host cells 1014 remains in collection chamber1022 (FIG. 10D). Quantitative container 1050 is then removed fromcollection container 1020 (FIG. 10E) and waste container 1090 isattached to quantitative container 1050 (FIG. 10F). A reagent is addedto collection chamber 1022 and force is then applied to filtrationdevice 1010 in a manner that pushes waste container 1090 into collectionchamber 1022 separating components or fractions 1015 of retainedbiofluid sample 1014 into waste chamber 1092 (FIG. 10G). Collectionchamber cap 1026 is opened (FIG. 10H), additional reagents are added tocollection chamber 1022 (FIG. 10I), and collection chamber cap 1026 isclosed (FIG. 10J). Force is then applied to filtration device 1010 in amanner that pushes waste container 1090 into collection chamber 1022separating further components or fractions 1015 of retained biofluidsample 1014 and mixing the flow through with the component or fractionsample already contained in waste chamber 1092 (FIG. 10K).

In another embodiment, a method of processing a biofluid sample using afiltration device 1110 comprises the step of depositing biofluid sample1112 into collection chamber 1122 of collection container 1120 (FIG.11A). After deposition of biofluid sample 1112, collection chamber cap1126 is removed and quantitative container 1150 (having plunger device1160 attached to it) is attached to collection container 1120 (FIG.11B). Filtration device 1110 is inverted (FIG. 11C) and a measuredamount of biofluid sample 1112 is collected in quantitative chamber 1152after being filtered by quantitative filter 1153 (FIG. 11D). Aftertransfer of measured amount of biofluid sample 1112, collectioncontainer 1120 is removed from quantitative container 1150 (havingplunger device 1160 attached to it) (FIG. 11E). If desired, collectionchamber cap 1126 can be attached to collection container 1120 (FIG.11E). Base 1154 with needle 1158 is removed and base 1154 without needleis secured to quantitative container 1150 (FIG. 11F). Quantitativecontainer 1150 (having plunger device 1160 attached to it) is thenplaced in centrifuge and components or fractions of measured amount ofbiofluid sample 1112 separated by application of force (FIG. 11G). Forceis then applied to plunger device 1160 in a manner that pushes plungerdevice 1160 into quantitative chamber 1152 (FIG. 11H). The applicationof force pushes biofluid sample 1112 through filter device 1140 therebyseparating components or fractions of biofluid sample 1112 into adefined volume of filtered components or fraction 916 collected inplunger chamber 1163 and retained biofluid sample comprising host cells1114 remains in quantitative chamber 1152 (FIG. 11H). Plunger device1160 is then detached from quantitative container 1150 by removal ofplunger attachment 1170 (FIG. 11I). If desired, both filtered componentsor fraction 1116 and retained biofluid sample 1114 can then be furtherprocessed.

In one embodiment, a method of processing a biofluid sample using afiltration device 1210 comprises the step of depositing biofluid sample1212 into collection chamber 1222 of collection container 1220 usingcollection device 1230 (FIG. 12A). After depositing biofluid sample 1212to collection chamber 1222, collection device 1230 is removed andcollection chamber cap 1226 is secured to collection container 1220(FIG. 12B). Force is then applied by squeezing the wall of collectioncontainer 1220 (FIG. 12C). The application of force pushes biofluidsample 1212 through filter device 1240 thereby separating components orfractions of biofluid sample 1212 into a defined volume of filteredcomponents or fraction 1216 collected in quantitative chamber 1252 andretained biofluid sample comprising host cells 1214 remains incollection chamber 1222 (FIG. 12C). Quantitative container 1250 is thenremoved from collection container 1220 and quantitative chamber cap 1276is attached to quantitative container 1250 (FIG. 12D). Filtered biofluidsample 1216 can then be dispensed from quantitative container 1250 byremoving quantitative chamber cap 1276 and applying force by squeezingthe wall of quantitative container 1250, thereby dispensing filteredbiofluid sample 1216 via nozzle on quantitative chamber dispenser 1278(FIG. 12F).

Yet another embodiment is illustrated in FIGS. 13A-D. In thisembodiment, the filtration device 1310 generally includes a collectioncontainer 1320 with a flexible wall 1321 defining a collection chamber1322 therewithin, a filter device 1340 at the bottom of the collectionchamber 1322, a collection device 1330 detachable from the mouth 1327 ofthe collection chamber 1322, a collection chamber cap 1326 configured toselectively seal the collection chamber 1322, a quantitative chamberdispenser 1378 in fluid communication with the collection chamber 1322through the filter device 1340 and downstream from the filter device1340, and a dispenser cap 1379 detachable from the quantitative chamberdispenser 1378. The collection device 1330 is preferably a funnel with astem 1331 that inserts and attaches within the mouth 1327 of thecollection chamber 1322 by frictional engagement, snap feature, othertemporary attachment means. The collection device 1330 is sufficientlysized and shaped to collect a biofluid sample 1312, e.g., saliva, urine,or other bodily fluid. The biofluid sample 1312 is deposited into thecollection device 1330 and drained into the collection chamber 1322through the stem 1331 inserted into the mouth 1327. Generally, duringthe collection of the biofluid sample 1312, the dispenser cap 1379 isseated over the quantitative chamber dispenser 1378 to seal the orifice1377. The dispenser cap 1379 may be connected to the quantitativechamber dispenser 1378 or other part of the filtration device 1310 by aliving hinge, lanyard, or other connecting device to keep the dispensercap 1379 in proximity to the filtration device 1310. Once the biofluidsample 1312 is collected, the collection device 1330 is detached, andthe collection chamber cap 1326 is sealed to the mouth 1327 to seal thecollection chamber 1322 from above. The collection chamber cap 1326 maybe any variety of caps, such as the bung stopper type cap connected tothe collection container 1320 by a living hinge, lanyard, or otherconnection means.

Once the biofluid sample 1312 has been collected and contained with thecollection chamber 1322, and the collection chamber 1322 sealed byclosing the collection chamber cap 1326, the user applies a pinching orsqueezing force on the collection chamber 1322 causing the flexible wall1321 to collapse and reduce the volume of the collection chamber 1322.The reduction in volume and accompanying increase in pressure forces thebiofluid sample 1312 through the filter device 1340 which captures much,if not all, the debris 1341 within the biofluid sample 1312. Thefiltered biofluid sample 1316 is collected within the nozzle 1375 of thequantitative chamber dispenser 1378 downstream of the filter device1340. Upon detachment of the dispenser cap 1379 from the collectioncontainer 1320, the user may selectively apply pressure to the flexiblewall 1321 of the collection container 1320 to force the flow of thefiltered biofluid sample 1316 out of the orifice 1377, preferably in apredetermined droplet size controlled at least in part by the orifice1377 diameter. The droplets of filtered biofluid sample 1316 may beinstilled on a lateral flow device 1351, as illustrated in FIG. 13D, orcollected for later analysis or immediate freezing in a storage device,or applied to a diagnostic device. The volume of each drop of filteredbiofluid sample 1316 is controlled by the diameter of the orifice. Inone example embodiment, six drops can equal approximately 100microliters, but may vary from 1 microliter to 200 microliters.

The advantage of filtering the biofluid sample 1312 is that a typicalbiofluid sample 1312 has a large number of contaminants; for example,saliva generally has food and other debris and detritus, as well asbacteria and human cells that negatively affect the assay. Furtheradvantages include the elimination or reduction of centrifugation andcold chain logistics. The filter device 1340 is selected to removeundesired components within the feed (biofluid sample 1312) to produce ahigher purity filtrate (filtered biofluid sample 1316). Squeezing thecollection chamber 1322 creates the necessary difference in pressureacross the filter device 1340 to force the feed through the filterdevice 1340. Diseases with detectable biomarkers within the filteredbiofluid sample 1316 (such as in salivary analytes) are detectable usingthe present device 1310, such as malaria, periodontal disease, andcortisol stress, without interference from contaminants. The types ofanalysis may include, but are not limited to, human and bacterial DNApurification and quantitation by RT-PCR and a biomarker assay. Twocommon salivary biomarkers are cortisol (a steroid) and interleukin 1β(a protein).

A kit may include the filter device 1310, collection device 1330 and acontainer of cell lysis solution that may be placed in fluidcommunication with either the orifice 1377 or the mouth 1327 forintroducing the cell lysis solution into the collection chamber 1322. Inone method, the user may apply a squeezing force on the flexible wall1321 of the collection chamber 1322 to force out substantially all thebiofluid sample 1312, leaving the debris 1341 in or on the filter device1340. The orifice 1377 is submerged in the cell lysis solution or thecell lysis solution container is connected to the quantitativecollection dispenser 1378. The user releases the squeezing force appliedto the collection chamber 1322 so that the wall 1321 is permitted torebound to its original shaped, thereby producing a vacuum within thecollection chamber 1322 that draws the cell lysis solution through thefilter device 1340 and into the collection chamber 1322, where the celllysis solution extract DNA and such from the cells remaining within thecollection chamber 1322. Once the cells have been processed within thecell lysis solution, the solution may be pushed back through the filterfor collection and analysis.

The present filtering device 1310 provides a rapid, cost effective,non-invasive collection and clean-up of saliva (e.g., reduction ofcontaminants, matrix effects, etc.) for early detection of Malariabiomarkers (e.g., pfHRP2, etc.). Clean or filtered saliva offers severaladvantages over blood no cultural and/or religious biases associatedwith collection of blood, a reduced biohazard to worker, non-invasive,easy and in-field usable, and it requires minimal or no training. Thispermits the early and accurate diagnosis of Malaria at thepoint-of-care, within the recommended 24 hour window after the onset offever. It is important to process a biofluid sample to eliminatebiomarker stability issues, contaminants (e.g., cells, mucins, etc.),and matrix effects (e.g., viscosity), which is easily carried out in thefield using the present filtering device 1310, without the use of coldchain logistics or centrifugation. Using the present filtering device1310, in less than 10 seconds after collection the viscosity issignificantly reduced and the saliva filtered which readies the samplefor immediate testing.

Aspects of the present specification may also be described as follows:

-   1. A filtration device comprising    -   a) a collection container comprising a collection chamber and a        filter device comprising a filter mount, a filter, a port, a        one-way check valve, and O-ring; and    -   b) a quantitative container comprising a quantitative chamber        and a base;        -   wherein the quantitative container is removably attached to            the collection container and        -   wherein the quantitative container is configured to move            into the collection chamber upon the application of force.-   2. The filtration device according to embodiment 1, wherein the    collection container includes a collection chamber cap attached to    the collection container.-   3. The filtration device according to embodiment 1 or 2, wherein the    collection container includes a collection chamber cap not attached    to the collection container.-   4. The filtration device according to any one of embodiments 1-3,    wherein the base is removable.-   5. The filtration device according to any one of embodiments 1-4,    wherein the filter has a pore size of about 0.2 μm to about 50.0 μm.-   6. The filtration device according to any one of embodiments 1-5,    wherein the quantitative chamber has a volume of about 0.5 mL to    about 5.0 mL.-   7. The filtration device according to any one of embodiments 1-6,    wherein the quantitative chamber has a volume of 1 mL.-   8. A filtration device comprising    -   a) a quantitative container comprising a quantitative chamber        and a base; and    -   b) a plunger device comprising a plunger including a channel, a        valve, and a plunger O-ring, and a plunger attachment including        a plunger attachment face seal.    -   wherein the plunger device is removably attached to the        quantitative container and wherein the plunger device is        configured to move into the quantitative chamber upon the        application of force.-   9. The filtration device according to embodiment 8, wherein the base    is removable.-   10. The filtration device according to embodiment 8 or 9, wherein    the quantitative chamber has a volume of about 0.5 mL to about 5.0    mL.-   11. The filtration device according to any one of embodiments 8-10,    wherein the quantitative chamber has a volume of 1 mL.-   12. The filtration device according to any one of embodiments 8-11,    wherein the valve is a duck-bill valve.-   13. The filtration device according to any one of embodiments 8-12,    further comprising a needle device attached to the base.-   14. The filtration device according to embodiment 13, wherein the    needle device includes a needle having a diameter between about 0.1    mm to about 2.0 mm.-   15. The filtration device according to embodiment 13 or 14, wherein    the needle device includes a needle filter.-   16. The filtration device according to embodiment 15, wherein the    needle filter has a pore size of about 0.2 μm to about 50.0 μm.-   17. A filtration device comprising    -   a) a quantitative container comprising a quantitative chamber, a        quantitative filter, and a base including a base needle; and    -   b) a plunger device comprising a plunger including a plunger        O-ring, a plunger filter, a plunger chamber, and a plunger        attachment including a plunger attachment face seal.    -   wherein the plunger device is removably attached to the        quantitative container and wherein the plunger device is        configured to move into the quantitative chamber upon the        application of force.-   18. The filtration device according to embodiment 17, wherein the    quantitative chamber has a volume of about 0.5 mL to about 5.0 mL.-   19. The filtration device according to embodiment 18, wherein the    quantitative chamber has a volume of 1 mL.-   20. The filtration device according to any one of embodiments 17-19,    wherein the quantitative filter has a pore size of about 0.2 μm to    about 50.0 μm.-   21. The filtration device according to any one of embodiments 17-20,    wherein the base needle has a diameter between about 1.0 mm to about    10.0 mm.-   22. The filtration device according to any one of embodiments 17-21,    wherein the base needle includes a base needle filter.-   23. The filtration device according to any one of embodiments 17-22,    wherein the base needle filter has a pore size of about 0.2 μm to    about 50.0 μm.-   24. The filtration device according to any one of embodiments 17-23,    wherein the plunger chamber has a volume of about 0.5 mL to about    5.0 mL.-   25. The filtration device according to embodiment 24, wherein the    plunger chamber has a volume of 1 mL.-   26. The filtration device according to any one of embodiments 17-25,    wherein the plunger filter has a pore size of about 0.2 μm to about    50.0 μm.-   27. The filtration device according to any one of embodiments 17-26,    further comprising a collection container comprising a collection    chamber, wherein the collection container is removably attached to    the quantitative container.-   28. The filtration device according to embodiment 27, wherein the    collection chamber has a volume of about 0.5 mL to about 10.0 mL.-   29. The filtration device according to embodiment 28, wherein the    collection chamber has a volume of about 1 mL to about 5.0 mL.-   30. A filtration device comprising    -   a) a collection container comprising a collection chamber and a        filter device comprising a filter mount, a filter, and O-ring;        and    -   b) a quantitative container comprising a quantitative chamber;        -   wherein the quantitative container is removably attached to            the collection container.-   31. The filtration device according to embodiment 30, wherein the    collection container includes a collection chamber cap attached to    the collection container.-   32. The filtration device according to embodiment 30 or 31, wherein    the collection container includes a collection chamber cap not    attached to the collection container.-   33. The filtration device according to any one of embodiments 30-32,    wherein the filter has a pore size of about 0.2 μm to about 50.0 μm.-   34. The filtration device according to any one of embodiments 30-33,    wherein the quantitative chamber has a volume of about 0.5 mL to    about 5.0 mL.-   35. The filtration device according to any one of embodiments 30-34,    wherein the quantitative chamber has a volume of 1 mL.-   36. The filtration device according to any one of embodiments 30-35,    wherein the quantitative chamber further comprises a quantitative    chamber dispenser.-   37. The filtration device according to any one of embodiments 1-36,    wherein the collection container is designed to have rigid walls.-   38. The filtration device according to any one of embodiments 1-36,    wherein the collection container is designed to have flexible walls.-   39. A method of processing a biofluid sample using a filtration    device as defined in any one of embodiments 1-16 or 30-38, the    method comprising the steps of:    -   a) depositing a biofluid sample into the collection chamber of        the filtration device; and    -   b) applying a force to the filtration device whereby the        biofluid sample passes through the filter of the collection        chamber, a defined volume of filtered biofluid sample is        collected in the quantitative chamber, and a retained biofluid        sample remains in the collection chamber.-   40. The method according to embodiment 39, wherein the force is    applied in a manner that moves a quantitation chamber into a    collection chamber of a collection container 41. The method    according to embodiment 39, wherein the force is applied in a manner    that squeezes the walls of a quantitative container.-   41. A method of processing a biofluid sample using a filtration    device as defined in any one of embodiments 1-16 or 30-38, the    method comprising the steps of:    -   a) depositing a biofluid sample into the collection chamber of        the filtration device;    -   b) applying a force to the filtration device whereby the        biofluid sample passes through the filter of the collection        chamber, a filtered biofluid sample is collected in the        quantitative chamber, and a retained biofluid sample is present        in the collection chamber;    -   c) removing the quantitative sample comprising the filtered        biofluid sample;    -   d) attaching a plunger device comprising a plunger and a channel        to the quantitative chamber; and    -   e) processing the filtered biofluid sample by the addition of        suitable reagents using the channel.-   42. The method according to embodiment 41, wherein step (e) is    repeated one or more times with the same or different reagents.-   43. The method according to embodiment 41 or 42, wherein the force    is applied in a manner that moves a quantitation chamber into a    collection chamber of a collection container 44. The method    according to embodiment 41 or 42, wherein the force is applied in a    manner that squeezes the walls of a quantitative container.-   45. A method of processing a biofluid sample using a filtration    device as defined in any one of embodiments 1-16 or 30-38, the    method comprising the steps of:    -   a) depositing a biofluid sample into the collection chamber of        the filtration device;    -   b) applying a force to the filtration device whereby the        biofluid sample passes through the filter of the collection        chamber, a filtered biofluid sample is collected in a        quantitative chamber, and a retained biofluid sample is present        in the collection chamber;    -   c) removing the quantitative sample comprising the filtered        biofluid sample;    -   d) attaching a plunger device comprising a plunger and a channel        to the quantitative chamber;    -   e) processing the filtered biofluid sample by the addition of        suitable reagents using the channel;    -   f) attaching the needle device comprising a needle and porous        filter to the quantitative chamber; and    -   g) expelling the processes filtered biofluid sample from the        quantitative chamber into a collection tube using the plunger.-   46. The method according to embodiment 38, wherein step (e) may be    repeated one or more times with the same or different reagents.-   47. The method according to embodiment 45 or 46, wherein the force    is applied in a manner that moves a quantitation chamber into a    collection chamber of a collection container-   48. The method according to embodiment 45 or 46, wherein the force    is applied in a manner that squeezes the walls of a quantitative    container.-   49. A method of processing a biofluid sample using a filtration    device, the method comprising the steps of:    -   a) attaching a collection container comprising a biofluid sample        to the filtration device as defined in any one of embodiments        17-29, 37 or 38;    -   b) transferring an amount of the biofluid sample to the        quantitative chamber;    -   c) removing the collection container from the filtration device;    -   d) applying a force to the filtration device whereby the        biofluid sample passes through the quantitative filter of the        quantitative container, a filtered biofluid sample is collected        in the plunger chamber, and a retained biofluid sample remains        in the quantitative chamber.-   50. The method according to embodiment 42, further comprising the    step of applying a force to the filtration device whereby the    biofluid sample is separated into two or more fractions within the    quantitative chamber, the step being performed before step (d).-   51. The method according to embodiment 49 or 50, wherein the force    is applied in a manner that moves a quantitation chamber into a    collection chamber of a collection container-   52. The method according to embodiment 49 or 50, wherein the force    is applied in a manner that squeezes the walls of a quantitative    container.-   53. A method of processing a biofluid sample using a filtration    device as defined in any one of embodiments 1-16 or 30-38, the    method comprising the steps of:    -   a) depositing a biofluid sample into the collection chamber of        the filtration device; and    -   b) applying a force to the filtration device whereby the        biofluid sample passes through the filter of the collection        chamber, a defined volume of filtered biofluid sample is        collected in the quantitative chamber, and a retained biofluid        sample remains in the collection chamber.-   54. The method according to embodiment 53, further comprising    step c) removing the quantitative container from the collection    container and attaching a quantitative chamber dispenser to the    quantitative container.-   55. The method according to embodiment 54, further comprising    step d) applying a force to the quantitative container whereby the    filtered biofluid sample passes from collection chamber to the    outside environment.-   56. The method according to any one of embodiments 53-55, wherein    the force in step b) is in a manner that squeezes the walls of a    quantitative container.-   57. The method according to embodiment 55, wherein the force in    step d) is in a manner that squeezes the walls of a quantitative    container.-   58. A system for processing a biofluid sample, the system comprising    a filtration device as defined in any one of embodiments 1-38, or:    -   a) a collection container comprising a collection chamber and a        filter device comprising a filter mount, a filter, a port, and        O-ring;    -   b) a quantitative container comprising a quantitative chamber        and base; and    -   c) a plunger device comprising a plunger including a channel, a        valve and a plunger O-ring, and a plunger attachment including a        plunger attachment face seal.-   59. The system according to embodiment 58, wherein the base is    removable.-   60. The system according to embodiment 58 or 59, further comprising    a needle device comprising a needle and a needle filter.-   61. The system according to any one of embodiments 58-60, further    comprising a waste container comprising a waste chamber.-   62. A system for processing a biofluid sample, the system comprising    a filtration device as defined in any one of embodiments 1-38, or:    -   a) a collection container comprising a collection chamber and a        filter device comprising a filter mount, a filter, a port, and        O-ring;    -   b) a quantitative container comprising a quantitative chamber        and base;    -   c) a waste container comprising a waste chamber;    -   d) a plunger device comprising a plunger including a channel, a        valve and a plunger O-ring, and a plunger attachment including a        plunger attachment face seal; and    -   e) a needle device comprising a needle and a needle filter.-   63. A system for processing a biofluid sample, the system comprising    a filtration device as defined in any one of embodiments 1-38, or:    -   a) a quantitative container comprising a quantitative chamber        and a base including a needle;    -   b) a plunger device comprising a plunger including a plunger        O-ring, a plunger filter, a plunger chamber, and a plunger        attachment including a plunger attachment face seal; and    -   c) a base without needle.-   64. The system according to embodiment 63, further comprising a    collection container comprising a collection chamber and collection    chamber cap.-   65. A system for processing a biofluid sample, the system comprising    a filtration device as defined in any one of embodiments 1-38, or:    -   a) a collection container comprising a collection chamber and        collection chamber cap;    -   b) a quantitative container comprising a quantitative chamber        and a base including a needle;    -   c) a plunger device comprising a plunger including a plunger        O-ring, a plunger filter, a plunger chamber, and a plunger        attachment including a plunger attachment face seal; and    -   d) a base without needle.-   66. A system for processing a biofluid sample, the system comprising    a filtration device as defined in any one of embodiments 1-38, or:    -   a) a collection container comprising a collection chamber and a        filter device comprising a filter mount, a filter, and O-ring;        and    -   b) a quantitative container comprising a quantitative chamber        and a quantitative chamber dispenser.-   67. The system according to embodiment 66, wherein the collection    container is designed to have flexible walls.-   68. The system according to embodiment 66 or 67, wherein the    quantitative container is designed to have flexible walls.

EXAMPLES

The following non-limiting examples are provided for illustrativepurposes only in order to facilitate a more complete understanding ofrepresentative embodiments now contemplated. These examples should notbe construed to limit any of the embodiments described in the presentspecification, including those pertaining to the filtration devicedisclosed herein, or methods or uses of the filtration device disclosedherein.

Example 1

This example demonstrates that depending on the filter used, differenttypes of component separation can be achieved.

A user prepared a filtration device by attaching a funnel to the openingof a collection chamber of a filtration device comprising a collectionchamber and a quantitative chamber. The filtration device contained aPVDF membrane with a mean pore size of 5 μm (Millipore). The userdeposited saliva into the collection chamber using the attached funnel.After the saliva was deposited into the collection chamber, the userremoved the funnel and attached a collection chamber cap to the opening,thereby sealing the collection chamber. The user then pushed thequantitative chamber into the collection chamber, forcing a defined 1 mLvolume of saliva to pass through the filter. After filtration, both thefiltered saliva sample and retained saliva sample were assayed for thepresence of bacterial and human cells. The results indicate that theretained saliva sample after filtration comprised only 17% the bacterialcontent (i.e., the amount which remained bound to the filter), while theremainder of the bacterial content passed through the filter.Conversely, the retained saliva sample comprised over 99% of the humancell content (i.e., the amount which remained bound to the filter),while only about 0.7% of the human cell content passed through thefilter. These results indicate that a PVDF membrane with a mean poresize of 5 μm was sufficient to separate bacterial contamination fromhuman cells which would be critical for procedures, such as, e.g.,genotyping using DNA sequences techniques.

A user prepared a filtration device by attaching a funnel to the openingof a collection chamber of a filtration device comprising a collectionchamber and a quantitative chamber. The filtration device contained acellulose membrane with a mean pore size of 5 μm (Sartorius). The userdeposited saliva into the collection chamber using the attached funnel.After the saliva was deposited into the collection chamber, the userremoved the funnel and attached a collection chamber cap to the opening,thereby sealing the collection chamber. The user then pushed thequantitative chamber into the collection chamber, forcing a defined 1 mLvolume of saliva to pass through the filter. After filtration, both thefiltered saliva sample and retained saliva sample were assayed for thepresence of bacterial and human cells. The results indicate that theretained saliva sample comprised 96.5% of the bacterial content (i.e.,the amount which remained bound to the filter), with only a small amount(about 3.5%) of the bacterial content passed through the filter.Similarly, the retained saliva sample comprised over 98% of the humancell content (i.e., the amount which remained bound to the filter),while only about 1.6% of the human cell content passed through thefilter. These results indicate that a cellulose membrane with a meanpore size of 5 μm was very effective at filtering all cellular contentfrom whole saliva, but not effective in separating bacterial and humancells. Thereby such a filter membrane would not be suitable forgenotyping applications where purity of human DNA is of paramountimportance. However, it would be critical for procedures, such as, e.g.,assays designed to detect the presence of a compound (analyte) wherepresence of cells can interfere and lead to false positive results.

Example 2

This example describes how to use a filtration device disclosed hereinto filter a biofluid sample. A user prepares a filtration device byattaching a funnel to the opening of a collection chamber of afiltration device comprising a collection chamber and a quantitativechamber. The user hands the prepared filtration device to a subject andasks the subject to deposit saliva into the collection chamber using theattached funnel. After the saliva is deposited into the collectionchamber, the user removes the funnel and attaches a collection chambercap to the opening, thereby sealing the collection chamber. The userthen pushes the quantitative chamber into the collection chamber,forcing a defined 1 mL volume of saliva to pass through the filter, andthe filtered saliva is collected in the quantitative chamber of thequantitative container. The filter retains debris and othercontaminating material behind in the collection chamber. Afterfiltration, a defined volume of filtered saliva sample is collected inthe quantitative chamber and a retained saliva sample comprising hostcells is retained on the filter of the collection chamber.

The filtered saliva sample can now be used to any number of diagnosticassays used to detect the presence or absence of a compound orcompounds. For example, the filtered saliva sample can be tested for thepresence of cortisol, testosterone, leptin or C-Reactive Protein (CRP).For example, salivary cortisol was shown to be a good prognosticindicator of Major depressive disorder (MD) in the youth population atlarge that can aid the detection of at-risk groups. MD is a debilitatingpublic mental health problem with severe societal and personal costsattached. Dysregulated cortisol rhythms and elevated morning and eveningcortisol have consistently been reported as a risk factor for, orconsequence of, MD. By facilitating filtering of whole saliva duringearly AM and late night in at the point-of-care, an individual can forgoregular visits to the clinic for sample collection.

A device that simultaneously achieves separation of debris and othercontaminating material from saliva at point-of-care has broad utility inlife sciences. It allows users to assess levels of a large number ofcompounds useful as markers in the diagnosis of a wide variety ofdisease all with one device. Furthermore, the quantitative collection ofcell-free saliva will facilitate standardization of all diagnosticassays in that individual and comparing it to other individuals forpurposes of targeted therapy or epidemiological studies.

Example 3

This example describes how to use a filtration device disclosed hereinto filter a biofluid sample. A user prepares a filtration device byattaching a funnel to the opening of a collection chamber of afiltration device comprising a collection chamber and a quantitativechamber. The user hands the prepared filtration device to a subject andasks the subject to deposit saliva into the collection chamber using theattached funnel. After the saliva is deposited into the collectionchamber, the user removes the funnel and attaches a collection chambercap to the opening, thereby sealing the collection chamber. The userthen squeezes the wall of the collection container, forcing saliva topass through the filter, and the filtered saliva is collected in thequantitative chamber of the quantitative container. After thefiltration, a volume of filtered saliva sample is collected in thequantitative chamber and a retained saliva sample comprising host cells,debris and other contaminating material is retained on the filter of thecollection chamber.

The filtered saliva sample can now be used to any number of diagnosticassays used to detect the presence or absence of a compound or compoundsas described in Example 2.

A device that simultaneously achieves separation of debris and othercontaminating material from saliva at point-of-care has broad utility inlife sciences. It allows users to assess levels of a large number ofcompounds useful as markers in the diagnosis of a wide variety ofdisease all with one device. Furthermore, the quantitative collection ofcell-free saliva will facilitate standardization of all diagnosticassays in that individual and comparing it to other individuals forpurposes of targeted therapy or epidemiological studies.

Example 4

This example describes how to use a filtration device disclosed hereinto filter a biofluid sample. A user prepares a filtration device byattaching a funnel to the opening of a collection chamber of afiltration device comprising a collection chamber and a quantitativechamber. The user hands the prepared filtration device to a subject andasks the subject to deposit saliva into the collection chamber using theattached funnel. After the saliva is deposited into the collectionchamber, the user removes the funnel and attaches a collection chambercap to the opening, thereby sealing the collection chamber. The userthen pushes the quantitative chamber into the collection chamber,forcing a defined 1 mL volume of saliva to pass through the filter thatallows contaminating bacteria and/or infectious agents smaller than thefilter pore size to pass through, while retaining human cells behind inthe collection chamber. After the filtration, a defined volume offiltered saliva sample (containing contaminating bacteria and/or anyinfectious agents) is collected in the quantitative chamber and aretained saliva sample comprising host cells is retained on the filterof the collection chamber.

To process the filtered saliva sample in the quantitative chamber, theuser removes the quantitative chamber comprising the filtered salivasample and attaches a plunger device comprising a plunger and channel asdisclosed herein. The user then adds reagents such as lysis buffer withDNA binding beads to the saliva sample using the channel running throughthe plunger and mixes the added reagents and saliva by inverting andmixing the contents, allowing DNA released from the infectious agents inthe chamber to bind to the beads. Depending on the processing desired,the mixed sample may then be chilled on ice, heated in a water bath orincubator, or have additional reagents added.

To isolate DNA from this mixture, the user can add a needle devicedisclosed herein. The user attaches the needle device to the bottom ofthe quantitative chamber and then expels the mixed sample containing thebead-bound DNA into a collection tube. The bead-bound DNA captured onthe filter is then washed and eluted using reagents and methods known inthe art. The processed filtered saliva sample can then be used orfurther processed or stored for subsequent use or further processing.

To process the retained saliva sample in the collection chambercontaining human cells, the user removes the quantitative chambercomprising the filtered saliva sample and attaches a waste chamber asdisclosed herein to the collection chamber. The user then pushes thewaste chamber into the collection chamber to filter any remainingbiofluid sample contained in the collection chamber. The user thenremoves the collection chamber cap, adds reagents (such as wash buffer)to the collection chamber containing pure human cells, and re-attachesthe collection chamber cap and repeats the filtration process, ensuringcleansing of the human cells from any remaining contaminating bacterialand/or infectious agents. The washing can be done two or more times oras required to purify the human cells from remnant contaminatingbacterial and/or infectious agents. Depending on the processing desired,the retained saliva sample with reagents may then be chilled on ice,heated in a water bath or incubator, and/or have addition reagentsadded. Depending on the processing desired, after processing of theretained saliva sample is complete, the user may then re-suspend thehuman cell on the filter in re-suspension buffered solution and transferthe elute into a clean tube. The eluted human cells can then be used orfurther processed or stored for subsequent use or further processing indownstream applications such as genotyping

A device that simultaneously achieves separation of human cells fromcontaminating bacteria and/or potential infectious agents in saliva atthe point-of-care has broad utility in life sciences. It allows users toassess human host genotype information as well as quantification and/oridentification of potential infections associated with that individual,all with one device. Furthermore, the quantitative collection ofcell-free saliva will facilitate standardization of all assays fordetermining infections in that individual and comparing it to otherindividuals for purposes of targeted therapy or epidemiological studies.

Example 5

This example describes how to use a filtration device disclosed hereinto filter a biofluid sample. A user prepares a filtration device byattaching a funnel to the opening of a collection chamber of afiltration device comprising a collection chamber and a quantitativechamber. The user hands the prepared filtration device to a subject andasks the subject to deposit saliva into the collection chamber using theattached funnel. After the saliva is deposited into the collectionchamber, the user removes the funnel and attaches a collection chambercap to the opening, thereby sealing the collection chamber. The userthen squeezes the wall of the collection container, forcing saliva topass through the filter, and the filtered saliva is collected in thequantitative chamber of the quantitative container. After thefiltration, a defined volume of filtered saliva sample is collected inthe quantitative chamber and a retained saliva sample comprising hostcells, debris and other contaminating material is retained on the filterof the collection chamber. The filter used will allow contaminatingbacteria and/or infectious agents smaller than the filter pore size topass through, while retaining human cells behind in the collectionchamber. After filtration, a volume of filtered saliva sample(containing contaminating bacteria and/or any infectious agents) iscollected in the quantitative chamber and a retained saliva samplecomprising host cells is retained on the filter of the collectionchamber.

Example 6

This example describes how to use a filtration device disclosed hereinto filter a biofluid sample. A user adds a whole blood sample to acollection chamber of a filtration device comprising a collectionchamber and a quantitative chamber. After the blood sample is depositedinto the collection chamber, the user attaches a quantitationchamber/plunger device to the collection chamber. The user then pushesdown the quantitation chamber/plunger device into the collectionchamber, thereby transferring a defined 2.5 mL volume of whole bloodinto the quantitative chamber through the base needle. The user thenremoves the collection chamber from the quantitation chamber/plungerdevice. The user then removes the base comprising the needle andreplaces it with a base without any needle. The user then places thequantitation chamber/plunger device in a microcentrifuge and applies aforce sufficient to separate the plasma from the blood cells. Aftercentrifugation, the user then pushes the plunger device down into thequantitative chamber up to the interface of plasma and blood cellfraction, which enables a defined 1 mL volume of plasma to pass throughthe plunger filter and into the plunger chamber. The blood cell fractionis retained in the quantitative chamber. The user then detaches theplunger device from the quantitative chamber by unsecuring thequantitate chamber cap. The plunger device comprising the plasma is thenfurther processed or stored until needed.

In closing, it is to be understood that although aspects of the presentspecification are highlighted by referring to specific embodiments, oneskilled in the art will readily appreciate that these disclosedembodiments are only illustrative of the principles of the subjectmatter disclosed herein. Therefore, it should be understood that thedisclosed subject matter is in no way limited to a particularmethodology, protocol, and/or reagent, etc., described herein. As such,various modifications or changes to or alternative configurations of thedisclosed subject matter can be made in accordance with the teachingsherein without departing from the spirit of the present specification.Lastly, the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention, which is defined solely by the claims.Accordingly, the present invention is not limited to that precisely asshown and described.

Certain embodiments of the present invention are described herein,including the best mode known to the inventor(s) for carrying out theinvention. Of course, variations on these described embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventor(s) expect skilled artisans to employsuch variations as appropriate, and the inventor(s) intend for thepresent invention to be practiced otherwise than specifically describedherein. Accordingly, this invention includes all modifications andequivalents of the subject matter recited in the claims appended heretoas permitted by applicable law. Moreover, any combination of theabove-described embodiments in all possible variations thereof isencompassed by the invention unless otherwise indicated herein orotherwise clearly contradicted by context.

Groupings of alternative embodiments, elements, or steps of the presentinvention are not to be construed as limitations. Each group member maybe referred to and claimed individually or in any combination with othergroup members disclosed herein. It is anticipated that one or moremembers of a group may be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is deemed to contain the group asmodified thus fulfilling the written description of all Markush groupsused in the appended claims.

Unless otherwise indicated, all numbers expressing a characteristic,item, quantity, parameter, property, term, and so forth used in thepresent specification and claims are to be understood as being modifiedin all instances by the term “about.” As used herein, the term “about”means that the characteristic, item, quantity, parameter, property, orterm so qualified encompasses a range of plus or minus ten percent aboveand below the value of the stated characteristic, item, quantity,parameter, property, or term. Accordingly, unless indicated to thecontrary, the numerical parameters set forth in the specification andattached claims are approximations that may vary. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical indication shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and values setting forth the broad scope ofthe invention are approximations, the numerical ranges and values setforth in the specific examples are reported as precisely as possible.Any numerical range or value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Recitation of numerical ranges ofvalues herein is merely intended to serve as a shorthand method ofreferring individually to each separate numerical value falling withinthe range. Unless otherwise indicated herein, each individual value of anumerical range is incorporated into the present specification as if itwere individually recited herein. Similarly, as used herein, unlessindicated to the contrary, the term “substantially” is a term of degreeintended to indicate an approximation of the characteristic, item,quantity, parameter, property, or term so qualified, encompassing arange that can be understood and construed by those of ordinary skill inthe art.

Use of the terms “may” or “can” in reference to an embodiment or aspectof an embodiment also carries with it the alternative meaning of “maynot” or “cannot.” As such, if the present specification discloses thatan embodiment or an aspect of an embodiment may be or can be included aspart of the inventive subject matter, then the negative limitation orexclusionary proviso is also explicitly meant, meaning that anembodiment or an aspect of an embodiment may not be or cannot beincluded as part of the inventive subject matter. In a similar manner,use of the term “optionally” in reference to an embodiment or aspect ofan embodiment means that such embodiment or aspect of the embodiment maybe included as part of the inventive subject matter or may not beincluded as part of the inventive subject matter. Whether such anegative limitation or exclusionary proviso applies will be based onwhether the negative limitation or exclusionary proviso is recited inthe claimed subject matter.

The terms “a,” “an,” “the” and similar references used in the context ofdescribing the present invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. Further, ordinal indicators—such as “first,” “second,” “third,”etc.—for identified elements are used to distinguish between theelements, and do not indicate or imply a required or limited number ofsuch elements, and do not indicate a particular position or order ofsuch elements unless otherwise specifically stated. All methodsdescribed herein can be performed in any suitable order unless otherwiseindicated herein or otherwise clearly contradicted by context. The useof any and all examples, or exemplary language (e.g., “such as”)provided herein is intended merely to better illuminate the presentinvention and does not pose a limitation on the scope of the inventionotherwise claimed. No language in the present specification should beconstrued as indicating any non-claimed element essential to thepractice of the invention.

When used in the claims, whether as filed or added per amendment, theopen-ended transitional term “comprising” (along with equivalentopen-ended transitional phrases thereof such as “including,”“containing” and “having”) encompasses all the expressly recitedelements, limitations, steps and/or features alone or in combinationwith un-recited subject matter; the named elements, limitations and/orfeatures are essential, but other unnamed elements, limitations and/orfeatures may be added and still form a construct within the scope of theclaim. Specific embodiments disclosed herein may be further limited inthe claims using the closed-ended transitional phrases “consisting of”or “consisting essentially of” in lieu of or as an amendment for“comprising.” When used in the claims, whether as filed or added peramendment, the closed-ended transitional phrase “consisting of” excludesany element, limitation, step, or feature not expressly recited in theclaims. The closed-ended transitional phrase “consisting essentially of”limits the scope of a claim to the expressly recited elements,limitations, steps and/or features and any other elements, limitations,steps and/or features that do not materially affect the basic and novelcharacteristic(s) of the claimed subject matter. Thus, the meaning ofthe open-ended transitional phrase “comprising” is being defined asencompassing all the specifically recited elements, limitations, stepsand/or features as well as any optional, additional unspecified ones.The meaning of the closed-ended transitional phrase “consisting of” isbeing defined as only including those elements, limitations, stepsand/or features specifically recited in the claim, whereas the meaningof the closed-ended transitional phrase “consisting essentially of” isbeing defined as only including those elements, limitations, stepsand/or features specifically recited in the claim and those elements,limitations, steps and/or features that do not materially affect thebasic and novel characteristic(s) of the claimed subject matter.Therefore, the open-ended transitional phrase “comprising” (along withequivalent open-ended transitional phrases thereof) includes within itsmeaning, as a limiting case, claimed subject matter specified by theclosed-ended transitional phrases “consisting of” or “consistingessentially of.” As such, embodiments described herein or so claimedwith the phrase “comprising” are expressly or inherently unambiguouslydescribed, enabled and supported herein for the phrases “consistingessentially of” and “consisting of.”

All patents, patent publications, and other publications referenced andidentified in the present specification are individually and expresslyincorporated herein by reference in their entirety for the purpose ofdescribing and disclosing, for example, the compositions andmethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents isbased on the information available to the applicants and does notconstitute any admission as to the correctness of the dates or contentsof these documents.

While aspects of the invention have been described with reference to atleast one exemplary embodiment, it is to be clearly understood by thoseskilled in the art that the invention is not limited thereto. Rather,the scope of the invention is to be interpreted only in conjunction withthe appended claims and it is made clear, here, that the inventor(s)believe that the claimed subject matter is the invention.

1. A filtration device for filtering debris from a biofluid sample togenerate a filtered biofluid sample, the filtration device comprising: acollection container comprising a collection chamber defined by aflexible wall, wherein an entirety of the flexible wall is flexible, amouth fluidly communicating with the collection chamber and formedthrough the collection container at a top end, and a filter devicedefining a bottom of the collection chamber; a quantitative containercomprising a quantitative chamber in fluid communication with the filterdevice with the filter device separating the collection chamber from thequantitative chamber, and an orifice formed through the quantitativecontainer; a collection chamber cap configured for selectively sealingthe mouth of the collection chamber; and a collection device detachablyengagable with the mouth of the collection container; wherein, abiofluid sample is capable of being introduced into the collectionchamber through the mouth via the detachably engagable collectiondevice; wherein, with the biofluid sample positioned within thecollection chamber and the collection chamber cap sealed over the mouth,the flexible wall of the collection container is capable of beingsqueezed to reduce the volume of the collection chamber and force thebiofluid sample through the filter device, the filtered biofluid samplethereafter being contained within the quantitative chamber.
 2. Thefiltration device according to claim 1, wherein the filter device has apore size of about 0.2 μm to about 50.0 μm.
 3. The filtration deviceaccording to claim 1, wherein the quantitative chamber has a volume ofabout 0.5 mL to about 5.0 mL.
 4. The filtration device according toclaim 1, wherein the quantitative chamber has a volume of 1 mL.
 5. Thefiltration device according to claim 1, wherein the quantitativecontainer is a nozzle converging to the orifice.
 6. The filtrationdevice according to claim 5, wherein the orifice has a diameter sized sothat the filtered biofluid sample drips through the orifice in droplets,each droplet volume ranging between 1 microliter to 200 microliters. 7.The filtration device according to claim 1, wherein, in use, thecollection device receives the biofluid sample and guides the biofluidsample into the mouth to be collected in the collection chamber.
 8. Thefiltration device according to claim 1, wherein the collection device isa funnel with a stem, the stem engaging the mouth when the funnel isattached to the collection container.
 9. The filtration device accordingto claim 1, wherein the collection chamber cap is connected to thecollection container through a collection chamber cap living hinge. 10.The filtration device according to claim 1, wherein the quantitativechamber further comprises a dispenser cap for selectively sealing theorifice.
 11. The filtration device according to claim 10, wherein thedispenser cap is connected to the quantitative container through adispenser cap living hinge.
 12. The filtration device according to claim10, wherein the dispenser cap seals the filtered biofluid sample withinthe quantitative chamber when the dispenser cap is connected to thequantitative container.
 13. A filtration device for filtering debrisfrom a biofluid sample to generate a filtered biofluid sample, thefiltration device comprising: a collection container comprising acollection chamber defined by a flexible wall, wherein an entirety ofthe flexible wall is flexible, a mouth fluidly communicating with thecollection chamber and formed through the collection container at a topend, and a filter device defining a bottom of the collection chamber; aquantitative container comprising a quantitative chamber in fluidcommunication with the filter device with the filter device separatingthe collection chamber from the quantitative chamber, and an orificeformed through the quantitative container; a collection chamber capconfigured for selectively sealing the mouth of the collection chamber;and a funnel-shaped collection device providing a stem configured fordetachable engagement with the mouth of the collection container;wherein, a biofluid sample is capable of being introduced into thecollection chamber through the mouth via the detachably engagablecollection device; and wherein, with the biofluid sample positionedwithin the collection chamber and the collection chamber cap sealed overthe mouth, the flexible wall of the collection container is capable ofbeing squeezed to reduce the volume of the collection chamber and forcethe biofluid sample through the filter device, the filtered biofluidsample thereafter being contained within the quantitative chamber. 14.The filtration device according to claim 13, wherein the orifice has adiameter sized so that the filtered biofluid sample drips through theorifice in droplets, each droplet volume ranging between 1 microliter to200 microliters.
 15. The filtration device according to claim 13,wherein the filter device has a pore size of about 0.2 μm to about 50.0μm.
 16. The filtration device according to claim 13, wherein thequantitative container is a nozzle converging to the orifice.
 17. Afiltration device for filtering debris from a biofluid sample togenerate a filtered biofluid sample, the filtration device comprising: acollection container comprising a collection chamber defined by aflexible wall, wherein an entirety of the flexible wall is flexible, amouth fluidly communicating with the collection chamber and formedthrough the collection container at a top end, and a filter devicedefining a bottom of the collection chamber; a quantitative containercomprising a quantitative chamber in fluid communication with the filterdevice with the filter device separating the collection chamber from thequantitative chamber, and an orifice formed through the quantitativecontainer; a dispenser cap configured for selectively sealing theorifice of the quantitative chamber; and a collection chamber capconfigured for selectively sealing the mouth of the collection chamber;wherein, a biofluid sample is capable of being introduced into thecollection chamber through the mouth; wherein, with the biofluid samplepositioned within the collection chamber and the collection chamber capsealed over the mouth, the flexible wall of the collection container iscapable of being squeezed to reduce the volume of the collection chamberand force the biofluid sample through the filter device, the filteredbiofluid sample thereafter being contained within the quantitativechamber.
 18. The filtration device according to claim 17, wherein theorifice has a diameter sized so that the filtered biofluid sample dripsthrough the orifice in droplets, each droplet volume ranging between 1microliter to 200 microliters.
 19. The filtration device according toclaim 17, wherein the filter device has a pore size of about 0.2 μm toabout 50.0 μm.
 20. The filtration device according to claim 17, whereinthe quantitative container is a nozzle converging to the orifice.